THE  LIBRARY 

OF 

THE  UNIVERSITY 
OF  CALIFORNIA 

LOS  ANGELES 


THE  PROTEOMORPHIC  THEORY  AND 
THE  NEW  MEDICINE 


ABBREVIATED    CHRONOLOGICAL    LIST   OF   THE 

MORE  IMPORTANT  SCIENTIFIC  AND  HISTORICAL 

WRITINGS  OF  HENRY  SMITH  WILLIAMS 

Field  Notes  of  a  Naturalist  (with  over  two  hundred  original  draw- 
ings), 1877-1880;  Nesting  Habits  of  the  Ruffed  Grouse,  1881;  Prairie 
Life  and  Prairie  Seasons,  1881;  A  Plea  for  the  Better  Observance 
of  Medical  Ethics,  1884;  Modern  Philosophy,  1885;  Idealism,  1886; 
Check  List  of  Iowa  Birds,  1887;  On  a  Case  of  Shock,  with  Observations 
in  the  Vaso-Motor  System,  1889;  The  Encephalic  Circulation  and  Its 
Relation  to  the  Mind,  1889;  The  Treatment  of  Haematoma  Auris, 
1889;  Some  Psycho-Somatic  Base  Lines,  1890;  Molecular  Dynamics  of 
the  Encephalon,  1890;  The  Dream  State  and  its  Psychic  Correlatives, 
1891;  A  Modern  Form  of  Insanity,  1892;  General  Paresis,  1892;  The 
Philosophy  of  Bird  Life  (2  vols.),  1892;  The  Prairie  Hen  and  Its 
Enemies  (illustrations  by  the  Author),  1892;  A  Modern  Angelo,  1892; 
The  Lesson  of  Heredity,  1892;  Can  the  Criminal  be  Reclaimed?  1893; 
Shall  We  Look  Forward  or  Backward  in  Dealing  with  the  Criminal?  1894; 
The  New  World  of  the  Microscope,  1895;  A  New  Form  of  Radiation 
(Roentgen  Rays),  1896;  Science  at  the  Close  of  the  Eighteenth  Cen- 
tury, 1897;  The  Progress  of  Chemistry  in  the  Nineteenth  Century,  1898; 
The  Progress  of  Physiology  in  the  Nineteenth  Century,  1898;  The  Prog- 
ress of  Medicine  in  the  Nineteenth  Century,  1899;  The  Story  of  Nine- 
teenth-Century Science,  1900;  The  Literature  of  Science,  1901;  The 
Marine  Biological  Laboratory  at  Naples,  1901;  Ernst  Haeckel  and  the 
New  Zoology,  1902;  Low-Temperature  Researches,  1902;  The  History 
of  the  Art  of  Writing  (4  vols.),  1903;  The  Royal  Society,  1903;  The 
Influence  of  Modern  Archaeological  Research  on  the  Scope  of  World 
History,  1903;  The  Historians'  History  of  the  World  (25  vols.,  edited 
with  the  cooperation  of  many  specialists),  1900-1905;  Prehistoric 
Science,  1904;  Galileo  and  the  New  Physics,  1904;  A  History  of  Science 
(5  vols.),  1904;  The  Conquest  of  Nature,  1905;  The  Conquest  of  Time 
and  Space,  1905;  Tribute  from  the  Vegetable  World,  1906;  Tribute 
from  the  Animal  World,  1906;  The  Science  of  Happiness,  1907;  Alcohol 
and  the  Individual,  1908;  Alcohol  and  the  Community,  1909;  The 
Scientific  Solution  of  the  Alcohol  Problem,  1909;  Every-Day  Science: 
The  story  of  man's  application  of  organized  knowledge  to  the  needs  of 
practical  life  (n  vols.),  1909;  How  the  Body  Fights  Disease,  1910; 
Civilization  (article  in  "Encyclopaedia  Britannica"),  1910;  The  Wonder- 
Working  Electron,  191 1 ;  To- Day's  Science  in  Europe,  191 1 ;  The  Wonders 
of  Science  in  Modern  Life  (10  vols.),  1912;  Miracles  of  Science,  1913; 
Metchnikoff  and  the  Search  for  the  Philosopher's  Stone,  1913;  Mastering 
the  Microbe,  1913;  Adding  Years  to  Your  Life,  1914;  The  Life  and  Work 
of  Luther  Burbank  (12  vols.),  1914;  Painless  Childbirth,  1914;  The 
Mechanism  of  Immunization,  1914;  Better  Brains  for  the  Race,  1914; 
Race  Breeding,  1914;  Mental  Obliquities,  1914;  The  Protein  Treatment 
of  Cancer  in  the  Light  of  the  Proteomorphic  Theory,  1915;  Detective 
Work  in  the  Blood  Stream,  1915;  Modern  Warfare,  1915;  The  Proteal 
Treatment  of  Cancer:  A  New  Therapeutic  Method  as  Interpreted  in  the 
Light  of  the  Proteomorphic  Theory,  1916;  Medicine  as  a  Machine 
Process,  1916;  The  Proteal  Treatment  of  Rheumatism,  1917;  Science 
and  Progress,  1917;  Why  Die  Before  Your  Time?  1917;  The  Proteomor- 
phic Theory  and  the  New  Medicine,  1918. 


THE 

PROTEOMORPHIC    THEORY 
AND  THE  NEW  MEDICINE 

AN    INTRODUCTION   TO    PROTEAL 
THERAPY 


BY 

HENRY  SMITH  WILLIAMS,  B.Sc.,  M.D.,  LL.D. 

Member  of  the  National  Committee  for  Mental  Hygiene,  and  of  the  Hygiene  Refer- 
ence Board  of  the  Life  Extension  Institute;  successively  Pathologist  to  the 
Iowa  State  Hospital  at  Independence;  Assistant  Physician  to  the 
Blackwell's  Island  and  Bloomingdale  Asylums,  and  Medical 
Superintendent  of  the  New  York  Infant  Asylum  and 
the  Randall's  Island  Hospitals,  New  York  City. 


NEW  YORK 
THE  GOODHUE  COMPANY 

1918 


COPYRIGHT,  1918, 
THE  GOODHUE  COMPANY 


QVC/ 

5-70 


35ooh 

The  Chart  of  a  Blazed  Trail  in  a  Virgin  Territory 

•ffs  Beofcateo  to 

ORRILLA  WEBSTER  WILLIAMS, 

Latter-day  exemplar  of  the  traditional  spirit  of  the  Roman 
matron  and  the  Spartan  mother,  from  whom  in  a  large  mea- 
sure the  present  explorer  acquired  by  inheritance  and  through 
childhood  training  the  mental,  moral,  and  physical  equipment 
that  made  possible  the  conception  and  the  successful  prose- 
cution of  a  pioneer  journey  not  lacking  in  obstacles. 


Q 
\M 

I 


CONTENTS 

PAGE 

F.OREWORD 9-24 

General  Analysis  of  Discoveries  Involved,  9 — The  Ter- 
minology of  the  New  Science,  13 — How  the  Proteals  are  Pre- 
pared, 14 — The  Practical  Administration  of  the  Proteals,  15 
— Development  of  the  Proteal  Method,  20 — Other  Non- 
Specific  Proteins,  21 — Scientific  Medicine  Versus  Empiri- 
cism, 22. 

CHAPTER  I 
THE  MECHANISM  OF  PROTEIN  HYDROLYSIS  AND  IMMUNIZATION —      25-79 

General  Statement  of  the  Proteomorphic  Theory,  25 — 
Facts  and  Theories  of  Immunity,  3O-?-Protein  Metabolism,  33 
— Proteolytic  Activities  of  the  Leucocyte,  43 — The  Leucocyte 
and  Bacterial  Proteins,  47 — Transplanting  Organs,  47 — 
Tracing  Blood  Relationship,  48 — How  the  Test  Fluids  are 
Developed,  50 — Man's  Remote  Relatives,  51 — The  Source 
of  Specific  Antibodies,  52 — The  Primordial  Leucocyte,  56 — 
The  Leucocyte  as  a  Microcosm,  61 — Antitoxins  and  New 
Chemical  Problems,  64 — New  Experimental  Evidence,  69 — 
The  Red  Corpuscle  as  Master  Immunizer,  70 — Specific 
Affinities  and  Antagonisms,  72 — Loss  and  Gain  Through  the 
Division  of  Labor,  76 — The  Coalition  Between  Red  Corpuscles 
and  White,  77. 

CHAPTER  II 
THE  PROTEOLYTIC  MECHANISM  IN  OPERATION. 80-106 

The  Blood  Corpuscles  and  Parenteral  Digestion  of  Proteins, 
80— The  Phenomena  of  Anaphylaxis,  83— The  Synthesis  of 
Protein,  88 — The  Leucocyte  Balance,  93 — Hormones  and  the 
Corpuscle-Balance,  97 — General  Therapeutic  Applications 
of  the  Proteomorphic  Therapy,  98 — Serums,  Vaccines,  and 
Direct  Cyto-Therapy,  103. 

CHAPTER  III 
THE  DISCOVERY  OF  THE  PROTEIN  PRINCIPLE  IN  THERAPEUTICS.  . .   107-126 

Influence  of  Radium  on  Neopolastic  Cells,  107 — Cor- 
relating Data  from  Many  Fields  of  Science,  108 — The  Formu- 
lation of  the  Proteomorphic  Theory,  108 — The  Ideal  of 
Chemo-Therapy,  109 — A  Bizarre  Shot-Gun  Formula,  m — 
Observed  Reactions  Interpreted  in  the  Light  of  the  Proteo- 
morphic Theory,  1 13 — New  Clinical  and  Laboratory  Investiga- 
tions, 115 — The  Protein  Principle  Demonstrated,  118 — 
Theory  Tested  by  Prophecy,  119 — Proteals  and  the  Malig- 
nant Neoplasm,  120 — Other  Remedial  Uses  of  the  Proteals, 
122 — Wide  Acceptance  in  Recent  Months  of  the  Principle  of 
the  Protein  Response  in  Therapeutics,  125. 
vii 


Vtii  CONTENTS 

CHAPTER  IV 

PAGE 

THE  SCIENCE  AND  ART  OF  PROTEAL  THERAPY 127-220 

Essentials  of  the  Protein  Response,  127 — Modification  of  the 
Leucocyte  Count,  135 — Blood  Changes  in  Tuberculosis,  139 
— Tuberculosis  and  Protein  Poisoning,  141 — An  Interpreta- 
tion of  Corpuscular  Action,  144 — Age  and  the  Blood  Count, 
151 — Further  Hints  as  to  Differential  Functions,  153 — Rel- 
ative Non-Toxicity  of  the  Proteals,  158— The  Preparation 
of  the  Proteals,  162 — Specific  Properties  of  Non-Specific 
Proteins,  165 — The  Administration  of  the  Proteals,  167 — 
Proteal  Treatment  of  Cancer,  169 — Wider  Applications  of 
Proteal  Therapy:  Rheumatoid  Conditions,  Asthma,  and 
Psoriasis,  174 — Dietetic  Anomalies  Explained,  177 — Proteals 
in  the  Hands  of  the  Practitioner,  179 — How  Theory  Explains 
Practise,  1 86— Proteal  Therapy  and  Tuberculosis,  188— 
Intestinal  Toxaemias  and  the  Anaemias  and  Leukaemias 
under  Proteal  Treatment,  196 — Blood  Changes  Tentatively 
Explained,  199 — A  Case  of  Leukaemia,  206 — Studying  the 
Blood  Smear,  211 — Intestinal  Toxaemias  and  the  Corpus- 
cular Balance,  214 — By  Way  of  Summary,  217. 

PART  II 

CANCER:   INTERPRETED   IN  THE   LIGHT  OF   THE   PROTEOMORPHIC 

THEORY  AND  THE  PROTEIN  RESPONSE 223-304 

The  Nature  of  Cancer,  223 — The  Origin  of  Cancer,  225 — 
The  Local  and  Surgical  Treatment  of  Malignant  Neoplasms, 
229 — Biological  Measures  in  the  Treatment  of  Cancer,  233 
—The  Evolution  of  the  Protein  Principle,  239— The  Protein 
Response  Interpreted,  247 — Vegetable  Proteins  in  Cancer 
Treatment,  251 — The  Blood  in  Cancer  Subjects,  259 — Cancer 
and  the  Lymphoid  System,  271 — Animal  Experimentation 
and  Proteal  Therapy,  276 — The  Prevention  and  Cure  of 
Cancer,  296. 


FOREWORD 

This  book  is  essentially  a  Monograph  detailing  the  author's 
personal  discoveries,  original  theories,  and  practical  experiences 
in  a  new  domain  of  therapeutics. 

It  presents  a  series  of  new  observations  and  certain  novel 
theories  of  which  it  may  unqualifiedly  be  affirmed  that  they  are 
important  if  valid. 

As  a  matter  of  course,  not  all  these  series  of  new  observations 
and  theories  are  on  the  same  plane,  either  of  importance,  of  orig- 
inality, or  of  verisimilitude.  It  will  be  "well,  therefore,  to  give 
a  preliminary  outline  of  both  theories  and  practical  discoveries, 
with  suggestions  as  to  their  relative  importance  in  the  estimate 
of  the  author.  Such  an  outline  will  be  of  value  to  the  reader, 
both  in  his  preliminary  appraisal  of  the  matter  presented  and 
in  orienting  his  detailed  study  of  the  evidence  as  given  in  the  text. 

First  of  all,  as  constituting  the  most  general  analysis,  I  would 
point  out  that  three  fundamental  new  discoveries  are  conceived 
to  be  represented.  These  are : 

(1)  A   physiological    discovery,   to  the   effect   that    (a)    the 
mononuclear  leucocytes  are  the  agents  vitally  concerned  in  begin- 
ning hydrolysis,  and  (b)  the  red  corpuscles  the  agents  concerned 
with  the  completion  of  decompounding  of  foreign  proteins  in  the 
parenteral  system.     This  is  the  essence  of  the  Proteomorphic 
theory. 

(2)  The  therapeutic  discovery  that  foreign  proteins  and  pro- 
tein by-products  introduced  hypodermically  into  the  parenteral 
system  constitute  antigens  that  stimulate  responsive  activities  of 
the  organism  of  such  character  as  to  aid  tremendously  in  the  fight 
of  the  organism  against  the  evil  effect  of  other  foreign  proteins 
of  whatever  character,  introduced  by  pathological  processes,  in- 
cluding (a)  the  proteins  associated  with  the  bodies  of  pathogenic 
bacteria,  (b)  heterologous  protein  products  associated  with  de- 
fective digestion  and  assimilation,  and   (c)  autologous  proteins 
associated  with  the  hyperplasia  of  various  organs,  including  the 
so-called   malignant  neoplasms.     This  conception,   in   itself   an 
application  of  the  Proteomorphic  principle,  furnishes  the  founda- 
tion for  Non-specific  Protein  Therapy  in  general  and  Proteal 
Therapy  in  particular. 

(3)  The  discovery  that  a  single  protein  or  combination  of  pro- 
teins used  therapeutically  cannot  usually  produce  optimum  re- 
sults, because  the  system  becomes  sated  or  immunized  and  no 

9 


10  FOREWORD 

longer  gives  a  maximum  response.  This  principle,  combined 
with  the  others,  furnishes  the  basis  for  Proteal  Therapy  as  at 
present  developed. 

The  first  of  these  discoveries  was  announced  by  the  writer  in 
American  Medicine  of  October  and  November,  1914 ;  the  second 
had  first  detailed  announcement  in  the  writer's  article  in  the  New 
York  Medical  Journal  of  October  2,  1915.  The  two  discoveries 
are  interlinked  and  associated,  but  not  necessarily  interdependent. 
Either  one  of  them  might  be  proved  fallacious  without  necessarily 
affecting  the  status  of  the  other.  But  if  both  should  be  shown 
to  be  true,  it  will  appear  that  corollaries  of  practical  importance 
are  associated  with  each  that  give  mutual  support  to  one  another. 
The  third  discovery  was  first  publicly  announced  in  a  Monograph 
issued  December  1,  1916,  under  title  of  The  Proteal  Treatment 
of  Cancer  and  Allied  Conditions. 

The  above  statement  of  principles  may  be  considered  as  a 
fundamental  analysis  or  summary  of  the  most  novel  contents  of 
this  book.  Let  me  now  make  an  analysis  of  a  slightly  more 
detailed  character,  outlining  the  observed  facts  that  appear  to 
give  support  to  one  or  the  other  of  these  principles,  and  the 
various  collateral  theories  associated  therewith. 

The  series  of  new  facts,  then,  cited  sequentially  somewhat  in 
the  order  of  their  discovery,  comprise  the  following : 

(1)  Certain  substances  administered  hypodermically  have  been 
observed  to  have  a  definite  influence  on  the  clinical  progress  of 
persons  suffering  from  inoperable  cancer  of  many  types.    These 
substances  include  extracts  of  plant  products  and  animal  products 
of  many  kinds ;  but  they  have  this  point  in  common — all  of  them 
contain  protein  or  the  products  of  partial  protein  hydrolysis. 

(2)  The  observed  modifications  in  cancer  subjects  through 
administration  of  these  substances  include:   Alleviation  of  pain, 
modification  of  discharge,  modification  in  the  tumor  itself,  and 
modification  in  the  general  health  and  mental  attitude  of  the 
patient. 

(3)  The  same  protein  substances,  administered  hypodermically, 
have  been  observed  to  benefit  markedly  cases  of  (a)  rheumatoid 
arthritis,    (1>)   pulmonary  tuberculosis,   (c)   pernicious  anaemia, 
(d)  intestinal  toxaemia,  (e)  leukaemia,  (f)  Graves'  disease,  (g) 
psoriasis,  (h)  asthma,  (i)  arteriosclerosis,  (j)  neurasthenia,  (k) 
primary  and  secondary  anaemias. 

(4)  The  clinical  betterment  of  these  cases  has  been  observed  to 
be  associated  with  blood  modifications  of  a  definite  and  pre- 
dictable character,  namely:  increase  of  haemoglobin,  increase  in 
number  of  red  corpuscles,  increase  of  large  mononuclear  leuco- 
cytes, increase  of  eosinophiles,  and  modification  of  numbers  of 
polunuclears  and  small  lymphocytes  in  the  direction  of  the  nor- 


FOREWORD  11 

mal;  also  with  conspicuous  qualitative  changes  in  the  direction 
of  the  normal. 

(5)  Physiological   changes,   including   rises   of   temperature, 
quickened  pulse,  and  a  chill  are  not  infrequently  associated  with 
the  administration  of  the  remedies  in  question,  suggesting  an 
anaphylactic  reaction,  not  known  to  be  produced  by  anything 
but  protein  or  its  products.     This  reaction  appears  not  to  be 
evoked  in  the  same  degree  by  partially  hydrolyzed  proteins. 

(6)  It  has  been  observed  that  a  condition  of  immunization 
appears  to  be  attained  sooner  or  later,  after  which  the  patient 
no  longer  responds  in  the  same  way  to  a  particular  protein; 
but  that  change  to  another  protein  may  bring  about  a  new  re- 
sponse, with  possibilities  of  cumulative  beneficial  effects. 

The  theories  on  which  these  observed  facts  are  explained  by 
the  present  writer  are  the  following: 

(1)  The  essential  point  of  contact  between  the  different  sub- 
stances   administered    hypodermically    is   their   protein    content 
(either  the  full  molecule  or  products  of  partial  hydrolysis). 

(2)  Any  foreign  protein  injected  into  the  parenteral  system 
serves  as  an  antigen  and  stimulates  the  defensive  mechanism  of 
the  body  to  the  production  of  antibodies  capable  of  hydrolyzing 
foreign  proteins  of  various  types. 

(3)  Such  antibodies  are  enzymic  in  character,  and  both  specific 
and  general  in  nature — that  is  to  say,  they  hydrolyze  the  par- 
ticular protein  injected,  but  also  other  foreign  proteins  if  present. 

(4)  The  proteins  of  cancer  are  in  a  sense  foreign  proteins  and 
fall  within  the  scope  of  action  of  the  enzymes  called  forth  by 
the    medical   protein   antigens.      The    degenerative    diseases   of 
middle  life  and  old  age  are  usually  associated  with  disturbances 
of  metabolism  involving  the  parenteral  invasion  of  foreign  pro- 
teins or  the  undue  retention  or  incomplete  catabolism  of  protein 
end  products.     Tuberculosis  falls  within  the  same  category  be- 
cause of  associated  secondary  infections  and  the  accumulation  of 
localized   foci  of  autologous  and  bacterial  proteins  subject  to 
hydrolysis  by  the  corpuscular  enzymes. 

(5)  The  mechanism  particularly  involved  in  the  production  of 
the  protein-hydrolyzing  enzymes  is  the  blood-forming  mechanism 
and  its  products,  the  white  and  red  corpuscles. 

(6)  The  general  province  of  the  white  corpuscles  is  to  deal 
with  the  full-sized  protein  molecule  or  its  early  cleavage  prod- 
ucts, and  the  province  of  the  red  corpuscles  is  to  deal  with  the 
end  products  of  polypeptid  order,  including  bodies  of  the  hypo- 
zanthin-zanthin-uric  acid-urea  series. 

(7)  The  condition  of  the  abnormal  hyperplasia  of  the  cells 
of  various  organs  of  the  body,  including  the  blood-forming  or- 
gans, the  coats  of  the  arteries,  and  the  cells  of  epithelial,  endo- 


12  FOREWORD 

thelial,  and  connective  tissues,  may  be  spoken  of  as  a  condition 
of  hyperproteomorphism  or  the  cancerous  condition.  All  such 
conditions  are  more  or  less  subject  to  clinical  and  physiological 
benefits  from  the  administration  of  protein  antigens — the  effect 
being  indirect,  and  conditioned  on  changes  in  corpuscular  num- 
bers or  enzymic  activities. 

(8)  Autolyzed  cancer  cells  themselves  serve  as  antigens,  stim- 
ulating the  blood-forming  mechanism,  but  ultimately,  in  unfavor- 
able cases,  leading  to  the  exhaustion  and  overpowering  of  this 
mechanism  through  over-stimulation  and  to  the  excessive  destruc- 
tion of  corpuscles.     Similar  stimulation  and  possible  exhaustion 
result  from  the  parenteral  presence  of  other  foreign  proteins, 
heterologous  or  autologous. 

(9)  Protein  antigens  as  a  whole  may  conveniently  be  spoken 
of  as  Proteantigens.     Considering  the  observed  action  of  these 
proteins  in  stimulating  the  increase  of  the  ranks  of  large  mono- 
cytes,  the  word  Monocytosins  may  be  used  as  a  synonym  for 
proteantigens.     A  more  general  and  perhaps  more  appropriate 
word  would  be  Cytogens.    It  is  convenient  to  refer  to  the  non- 
bacterial  vegetable  proteins,  now  for  the  first  time  used  as  thera- 
peutic proteantigens  or  cytogens,  under  the  name  of  Proteals. 
Animal  substances  such  as  white  of  egg  and  milk  albumen,  sim- 
ilarly used,  may  be  spoken  of  as  Proteils. 

It  goes  without  saying  that  the  essential  facts  as  to  the  action 
of  the  proteantigens  are  matters  of  chief  importance.  Theories 
are  necessarily  subordinate,  and  questions  of  terminology  need 
give  us  no  concern  whatever.  The  latter  are  suggested  here 
merely  as  matters  of  convenience. 

There  is  a  considerable  body  of  evidence  in  support  of  all  the 
observations  and  all  the  theories  above  cited ;  but  naturally  much 
more  evidence  for  some  than  others.  Beyond  saying  that  the 
evidence  is  based  on  a  first-hand  study  of  a  large  number  of 
cases,  and  on  a  fairly  extensive  series  of  microscopical  observa- 
tions, together  with  reports  from  a  large  group  of  associated 
physicians  in  various  parts  of  the  United  States,  I  shall  not 
attempt  to  summarize  it  here.  The  object  of  this  book  is  to 
present  the  evidence  somewhat  in  detail;  yet  even  here  the 
presentation  is  explicative  rather  than  argumentative.  I  have 
not  thought  it  expedient  to  cumber  the  text  with  long  lists  of 
repetitive  cases,  as  I  might  readily  have  done.  I  have  not  dupli- 
cated the  tabular  records  of  my  Monograph  of  1916  (of  which  a 
new  edition  will  appear  presently).  I  have  endeavored,  rather, 
to  summarize  the  salient  facts  and  theories  in  the  most  condensed 
form  consistent  with  clear  exposition. 

In  view  of  the  importance  of  the  subject,  I  venture  to  hope  that 
the  candid  reader  will  reserve  judgment  as  to  an  estimate  of 


FOREWORD  13 

both  facts  and  theories  until  he  has  attentively  considered  the 
evidence.  It  can  scarcely  be  doubted,  I  think,  that  the  principles 
of  action  of  the  white  and  red  corpuscles  and  of  bodily  response 
to  proteantigens  are  matters  of  fundamental  importance,  and  I 
think  also  that  the  evidence  in  favor  of  the  validity  of  these  prin- 
ciples is  of  so  cogent  a  character  that  it  cannot  be  dismissed 
without  a  full  and  candid  hearing. 

When  I  first  put  forward  the  Proteomorphic  Theory,  I  sug- 
gested that  it  opened  up  entirely  new  fields  of  cyto-therapy ;  and 
in  the  first  exposition  of  the  protein-antigen  hypothesis,  I  sug- 
gested that  the  new  method  must  stand  on  a  par  with  serum 
therapy  and  vaccine  therapy,  if  indeed  it  did  not  ultimately  largely 
supplant  these  methods.  Since  these  estimates  were  made,  in 
October,  1914,  and  October,  1915,  respectively,  a  great  mass  of 
new  evidence  has  been  collected,  all  seemingly  in  the  same  scale 
of  the  balance. 

Confidence  in  the  validity  of  the  predictions  just  noted  has 
grown  with  the  accumulation  of  new  evidence. 

Possibly  it  may  not  be  an  exaggeration — should  the  above  facts 
and  theories  be  demonstrated  to  have  validity — to  speak  of  the 
protein  response  as  constituting  the  most  comprehensive  thera- 
peutic action  known  to  modern  medicine. 

THE  TERMINOLOGY  OF  THE  NEW  SCIENCE 

In  the  Monograph  of  December  1,  1916,  I  cited  the  need  of  a 
new  terminology  for  convenience  in  referring  to  the  new  thera- 
peutics. I  suggested  the  comprehensive  term  Proteantigen  as  a 
family  name  for  all  types  of  proteins  used  as  antigens  in  thera- 
peutics. As  an  alternate  name,  I  suggested  the  word  Macrocy- 
tosin  (perhaps  Monocytosin  would  be  better),  made  appropriate 
by  the  observed  increase  of  large  monocytes  that  constitutes  an 
important  feature  of  the  protein  response. 

I  further  introduced  the  word  Proteal  as  a  generic  term  for 
vegetable  Proteantigens ;  on  a  par  with  the  familiar  words  Serum 
(proteantigens  derived  from  the  blood  of  animals)  and  Vaccine 
(proteantigens  of  bacterial  origin).  A  little  later  (April,  1917) 
in  medical  addresses  I  suggested  the  word  Proteil  as  an  addi- 
tional member  of  the  group,  applied  to  proteantigens  of  animal 
origin  other  than  serums — for  example,  protein  extracts  of  animal 
organs,  like  the  "autolysates"  of  Klinger  and  the  "X-Substance" 
of  Gwyer ;  preparations  of  milk  protein,  egg  protein,  and  the  like. 

It  was  in  the  Monograph  of  December  1,  1916,  also,  that  I 
first  publicly  enunciated  the  principle  (backed  at  that  time  by  a 
half-year  of  experimental  observation)  'that  it  is  necessary  to 
change  the  type  of  proteantigen  from  time  to  time,  in  order  to 


14  FOREWORD 

get  cumulative  and  optimum  therapeutic  effects — a  principle  of 
great  theoretical  interest  in  the  light  of  the  Proteomorphic 
Theory,  and  of  fundamental  importance  in  the  practical  admin- 
istration of  non-specific  protein  therapy. 

In  the  succeeding  pages  the  proteantigens  chiefly  referred  to 
are  Proteals  of  various  types.  These  non-toxic  vegetable  pro- 
teins, as  prepared  in  my  private  laboratory,  are  the  agents  with 
which  the  wide  therapeutic  possibilities  of  non-specific  protein 
therapy  and  the  essentials  of  the  physiological  response  on  which 
these  possibilities  are  conditioned  have  been  demonstrated  in 
my  hands  and  in  the  hands  of  associated  physicians  in  various 
parts  of  the  world.  Full  details  as  to  the  perfected  methods  of 
preparation  of  the  Proteals  hitherto  used  in  my  laboratory  are 
given  in  the  concluding  chapter  of  the  present  book. 

How  THE  PROTEALS  ARE  PREPARED 

It  is  desirable  to  call  attention  here  to  the  fact  that  two  dif- 
ferent types  of  protein  extracts  have  been  used,  one  containing 
the  unbroken  protein  molecule,  the  other  proteins  partially  hydro- 
lyzed.  The  former  were  used  almost  exclusively  until  late  in  the 
year  1916.  It  will  be  well  to  recall  that  the  results  attained  up 
to  that  time  (and  in  particular  the  blood  observations  recorded) 
are  ascribable  to  the  unbroken  protein  molecule. 

The  essential  procedure  consists  of  the  extraction  of  the  pro- 
tein from  the  ground  seed  or  other  vegetable  substance  with  a 
salt  solution ;  precipitation  of  the  protein  from  this  solution  with 
hydrochloric  or  acetic  acid ;  washing  with  distilled  water ;  and 
the  redissolving  of  the  relatively  pure  protein  with  sodium  hy- 
droxide. The  final  solution  is  standardized  by  testing  for  nitro- 
gen, so  that  as  ultimately  used  it  contains  two  per  cent,  protein, 
this  percentage,  however,  being  modified  in  various  experimental 
tests.  The  solution,  being  kept  slightly  alkaline,  can  be  sterilized 
by  heat  after  sealing  the  ampules  in  which  it  is  placed  for  safe 
and  convenient  subsequent  handling. 

The  proteins  thus  preserved  will,  of  course,  be  quite  inert  if 
given  by  the  mouth.  Administered  hypodermically  in  doses  of 
from  ten  to  sixty  minims  the  effects  are  striking  and  charac- 
teristic. They  include  a  certain  amount  of  local  erythema  at 
the  point  of  injection ;  a  feeling  of  giddiness ;  nausea,  malaise, 
rise  of  temperature,  and  a  more  or  less  pronounced  chill. 

These  familiar  anaphylactic  symptoms  vary  in  their  intensity 
with  different  patients,  and  are  not  produced  in  the  same  degree 
by  different  proteins.  The  protein  of  rape  seed,  for  example, 
produces  a  much  less  severe  general  reaction  than  the  protein  of 
alfalfa  seed. 


FOREWORD  15 

After  the  above-described  method  of  preparing  the  protein 
extracts  had  been  employed  for  several  months  in  my  laboratory, 
a  more  expeditious  method  was  devised,  the  essential  features 
of  which  consist  of  boiling  the  powdered  plant  products  for  from 
two  to  four  hours  in  a  very  dilute  solution  of  hydrochloric  acid 
(20  to  80  cubic  centimeters  of  10  per  cent,  hydrochloric  acid  to 
the  liter  of  water,  incorporating  50  to  100  grams  of  the  plant 
powder)  ;  filtering;  neutralizing  with  sodium  hydroxide;  refilter- 
ing;  standardizing  by  the  Kjeldahl  nitrogen  test;  sealing  in  the 
ampules,  and  sterilizing  for  three  days  discontinuously. 

This  extract  contains  more  extraneous  matter  (starch,  glucose, 
lipoids,  salts)  than  the  other,  but  if  properly  prepared  it  is  a 
perfectly  transparent  fluid,  varying  in  color  from  amber  to  claret 
according  to  the  specific  protein  content.  The  partially  hydro- 
lyzed  protein  (alkali  albumen,  proteose,  peptone)  does  not  coag- 
ulate on  heating,  but  is  partly  precipitated  by  alcohol.  Nitric  acid 
precipitates  it  in  part ;  the  precipitate  being  dissolved  on  boiling, 
to  reprecipitate  on  cooling  (the  familiar  test  for  proteoses). 

Proteals  thus  prepared  are  pleasant  to  administer,  and  as  a 
rule  produce  little  or  no  reaction,  and,  in  ordinary  dosage,  no  con- 
spicuous systemic  reaction.  No  case  of  anaphylactic  shock  from 
their  use  has  been  observed  by  me,  or  reported,  although  many 
thousand  ampules  of  Proteals  of  this  character  have  been  sent 
from  my  laboratory  to  physicians  in  all  parts  of  the  western 
hemisphere,  and  administered  to  a  large  aggregate  number  of 
patients  suffering  from  disturbances  of  protein  metabolism  asso- 
ciated with  anaemias,  intestinal  toxaemias,  neurasthenia,  rheuma- 
toid conditions,  arteriosclerosis,  cancer,  psoriasis,  asthma,  and 
tuberculosis. 

THE  PRACTICAL  ADMINISTRATION  OF  THE  PROTEALS 

A  few  words  about  the  practical  administration  of  the  Pro- 
teals  above  described  will  perhaps  be  of  service  to  the  physi- 
cian who  may  consult  this  book  without  having  time  or  inclina- 
tion to  read  the  more  elaborate  presentation  of  the  subject  which 
makes  up  the  chief  content  of  later  chapters. 

As  above  explained,  Proteals  are  non-toxic  vegetable  proteins 
in  sterile  saline  solution,  standardized  by  a  nitrogen  test.  They 
give  opportunity  for  the  application  of  non-specific  protein  ther- 
apy to  a  wide  range  of  maladies  associated  with  disturbed  protein 
metabolism,  with  or  without  bacterial  infection. 

The  name  Proteal  originated  with  me,  and  has  not  been  applied, 
so  far  as  I  know,  to  any  product  made  elsewhere  than  in  my  pri- 
vate laboratory.  There  is  no  restriction,  however,  on  the  use 
of  the  word  or  on  the  preparation  of  the  products  themselves. 
I  hope  presently  to  see  the  Proteals  made  in  Board-of-Health 


16  FOREWORD 

laboratories  everywhere,  as  certain  serums  and  vaccines  are  now 
made,  for  free  distribution  to  the  profession  for  treatment  of  the 
poor.  Meantime,  to  the  full  extent  of  my  personal  resources,  I 
shall  see  that  no  one  is  denied  the  benefactions  of  the  Proteal 
treatment  for  want  of  money. 

The  Proteals  hitherto  used  most  extensively,  as  supplied  from 
my  laboratory  to  several  hundred  physicians  in  various  parts  of 
the  world,  are  chiefly  those  made  from  Alfalfa  seed,  Alfalfa 
meal,  Mustard  seed,  Rape  seed,  Hemp  seed,  and  Millet  seed. 
Numerous  other  vegetable  materials  and  some  animal  materials 
have  been  tested  experimentally,  and  some  of  these  give  promise 
of  therapeutical  usefulness  as  suppliers  of  proteins.  Meantime, 
the  available  Proteals  (which  have  passed  entirely  beyond  the 
experimental  stage,  having  been  used  for  minimum  periods  of 
eighteen  months,  and  administered  to  hundreds  of  patients  in 
the  aggregate)  are  sufficiently  varied  to  meet  a  wide  range  of 
therapeutic  needs. 

The  Proteals  now  available,  as  prepared  in  my  laboratory,  are 
distinguished  merely  by  numbers — No.  29  contains  the  protein  of 
Alfalfa  meal ;  No.  36,  Mustard  seed  protein ;  No.  38,  Millet  seed 
protein ;  No.  39,  Alfalfa  seed  protein ;  No.  42,  Rape  seed  protein. 
No.  37  is  a  mixture  of  the  proteins  of  Mustard  and  Alfalfa ;  No. 
40,  a  mixture  of  Mustard  and  Rape  proteins ;  No.  45,  a  mixture 
of  proteins  of  Alfalfa  seed,  Alfalfa  meal,  and  Millet  seed ;  No. 
60,  a  mixture  of  proteins  of  Alfalfa  seed  and  Alfalfa  meal ;  No. 
65,  a  mixture  of  the  seed  proteins  of  Alfalfa,  Mustard,  Millet, 
and  Rape,  and  the  protein  of  Alfalfa  meal. 

A  newer  series  includes  proteins  of  Oats,  No.  50 ;  Potato,  No. 
61 ;  Wheat,  No.  62 ;  Carrot,  No.  63 ;  Flax,  No.  64 ;  Cotton,  No. 
66 ;  Red  Clover,  No.  67 ;  White  Clover,  No.  68 ;  Spinach,  No.  70. 

A  new  combination,  designated  No.  75,  includes  the  seed  pro- 
teins of  Red  Clover,  Cotton,  Hemp,  Flax,  and  Carrot.  A  mix- 
ture of  this  combination,  in  equal  parts  with  the  combination 
above  designated  as  No.  65,  gives  ten  types  of  protein  and  is 
designated  Proteal  No.  100. 

All  these  Proteals  are  standardized  on  the  basis  of  a  two- 
per  cent,  protein  solution,  as  above  detailed ;  and  the  dosage  and 
method  of  administration  are  substantially  the  same  for  all. 

Administration  of  the  Proteals  is  always  hypodermic,  prefer- 
ably subcutaneous  (not  intramuscular  or  intravenous).  The  in- 
jection may  advantageously  be  given  into  the  back  of  the  upper 
arm,  about  midway  between  elbow  and  shoulder.  Some  physi- 
cians prefer  the  gluteal  region.  If  properly  administered  in  suit- 
able doses,  the  injection  should  cause  very  little  local  irritation, 
and  practically  no  reaction,  local  or  general.  Patients  differ  con- 
siderably, however,  in  their  sensitiveness. 


FOREWORD  17 

The  technique  of  administration  is  simple.  It  is  well  to  steri- 
lize the  patient's  skin  by  touching  the  point  of  injection  with 
Tincture  of  Iodine  and  then  with  Alcohol.  Touch  the  neck  of 
the  ampule  with  a  file,  and  it  may  readily  be  broken.  Insert  a 
sterile  hypodermic  needle  and  withdraw  the  amount  of  the  in- 
tended dose.  A  partially  used  ampule  may  be  resealed  by  touch- 
ing the  neck  immediately  to  a  drop  of  melted  sealing  wax.  If 
contaminated,  the  extract  becomes  an  excellent  culture  medium 
and  must,  of  course,  be  discarded. 

The  initial  dose  of  any  Proteal  is  from  three  to  five  minims. 
Repeat  this  daily  or  on  alternate  days  until  three  or  four  doses 
have  been  given.  Thereafter,  if  there  has  been  no  severe  reac- 
tion, increase  the  dose  by  one  or  two  minims  with  each  adminis- 
tration until  a  satisfactory  dosage  is  established  for  the  particular 
case  in  hand. 

The  maximum  dose  varies  with  individual  cases  and  with  dif- 
ferent maladies. 

In  anaemias,  intestinal  toxaemias,  asthma,  and  tuberculosis, 
optimum  results  have  been  attained  with  a  maximum  dose  of  five 
to  ten  minims,  administered  on  alternate  days  for  a  more  or  less 
protracted  period.  Obstinate  cases  of  psoriasis  have  yielded  to  a 
similar  dosage. 

With  rheumatic  conditions,  and  especially  rheumatoid  arthritis, 
on  the  other  hand,  it  is  usually  desirable  to  advance  to  a  dosage 
of  fifteen  or  twenty  minims  at  least;  sometimes  to  twenty-five 
or  thirty  minims,  administered  on  alternate  days  or  even  daily. 

Maximum  doses  and  frequent  administration  are  usually  de- 
sirable, also,  to  get  optimum  and  cumulative  results,  in  cases  of 
cancer,  particularly  where  the  neoplasm  is  large. 

The  blood  count  furnishes  the  best  guide  to  dosage  in  admin- 
istering the  Proteals.  The  Proteal  response  is  essentially  a 
blood  reaction.  The  ideal  is  to  bring  the  haemoglobin  to  approxi- 
mately normal ;  the  red  corpuscle  count  to  normal  or  supernor- 
mal; and  the  average  leucocyte  count  to  seven  or  eight  thou- 
sand, with  the  differential  count  showing  polynuclears  relatively 
low,  and  large  mononuclears  advancing  to  high  supernormal — ten, 
fifteen,  or  twenty  per  cent,  of  the  total. 

Where  the  blood  count  is  not  available,  clinical  symptoms 
must,  of  course,  furnish  a  guide  to  dosage.  It  goes  without 
saying  that  the  administration  of  the  Proteals  gives  opportunity 
for  the  exercise  of  skill  and  judgment  on  the  part  of  the  prac- 
titioner. The  response  and  the  needs  of  each  individual  patient 
should  be  carefully  studied,  as  in  the  administration  of  any  other 
line  of  scientific  treatment. 

A  change  of  Proteals  from  time  to  time  is  essential  in  the 
treatment  of  most  protracted  cases,  in  order  to  secure  cumulative 


18  FOREWORD 

and  optimum  results.  A  measure  of  immunization  to  any  par- 
ticular type  of  protein  appears  to  be  developed  in  most  cases, 
after  periods  varying  from  a  few  weeks  to  several  months. 
A  change  of  Proteals  is  then  indicated.  Each  protein  appears  to 
produce  an  individual  response,  so  the  new  Proteal  should  be 
given  in  minimum  doses  at  first,  advancing  gradually  to  a  max- 
imum as  with  the  first  extract. 

The  possibility  that  a  change  of  Proteals  is  indicated  should 
always  be  considered  when  a  patient,  after  a  term  of  favorable 
progress,  appears  to  reach  a  static  period  short  of  the  desired 
optimum  of  improvement. 

The  wide  range  of  therapeutic  applicability  of  the  Proteals 
is  due  to  the  fact  that  their  response  is  a  non-specific  protein 
response,  directly  evoking  modifications  of  the  blood — as  re- 
gards both  its  corpuscular  elements  and  their  enzymic  activities — 
that  are  beneficial  to  the  entire  organism.  This  explains  the  ob- 
served anomaly  that  the  same  Proteal  may  be  administered  with 
benefit  in  conditions  so  widely  removed,  pathologically,  as  the 
anaemias,  intestinal  and  other  toxaemias,  arteriosclerosis,  rheuma- 
toid conditions,  asthma,  tuberculosis,  psoriasis,  and  cancer. 

There  are,  indeed,  few,  if  any,  conditions  involving  disturbed 
protein  metabolism  in  which  the  Proteals  may  not  be  appealed 
to  with  a  large  measure  of  confidence.  The  degree  of  improve- 
ment to  be  hoped  for  depends,  of  course,  on  the  conditions  of 
the  individual  case. 

The  particular  Proteal  to  be  selected  for  initial  use  in  any 
individual  case  is  to  some  extent  a  matter  of  experiment.  I  have 
pointed  out  that  the  Proteal  response  is  largely  non-specific.  Ob- 
servation shows  that  to  a  large  extent  the  different  Proteals  are 
therapeutically  interchangeable.  Often  it  seems  a  matter  of  in- 
difference as  to  which  one  is  selected.  Yet  there  are  specific 
differences  among  the  vegetable  proteins,  as  a  matter  of  course ; 
and  some  of  them  evoke  a  much  more  active  response  than 
others. 

I  have  suggested,  as  a  general  principle,  that  the  proteins  sup- 
plied by  food  products  will,  as  a  rule,  evoke  a  less  active  response 
than  the  proteins  of  vegetables  that  have  not  been  used  as  food 
by  our  race.  Experience  seems  to  justify  this  theory ;  for  I  have 
observed  that  proteins  of  the  food  cereals  (also  the  proteins 
of  milk  and  egg)  and  the  proteins  of  mustard  and  rape  seed  are 
less  active  in  therapeutic  response  than  the  proteins  of  millet 
seed  and  alfalfa. 

In  the  treatment  of  individual  cases,  guided  by  this  principle, 
I  am  likely  to  administer  Mustard  seed  protein  (Proteal  No. 
36)  or  Rape  seed  protein  (Proteal  No.  42)  or  their  combination 
(Proteal  No.  40)  in  the  initial  treatment  of  mild  anaemias,  with 


FOREWORD  19 

the  attendant  conditions  of  "general  debility,"  neurasthenia,  etc., 
where  a  general  tonic  effect  is  desired.  For  treatment  of  severe 
rheumatoid  conditions,  of  tuberculosis,  and  of  cancer,  I  turn  at 
once  to  a  Proteal  containing  Alfalfa  protein  (Proteals  No.  29, 
No.  39,  or  No.  60),  or  to  the  combination  of  proteins  of  Alfalfa 
seed,  Alfalfa  meal,  and  Millet,  as  represented  by  Proteal  No.  45. 
Not  infrequently  I  shift  from  one  Proteal  to  another,  experi- 
mentally, after  a  few  doses;  and  sometimes  I  have  found  that 
an  individual  patient  responds  far  better  to  one  type  of  protein 
than  to  another,  regardless  of  the  type  of  malady. 

In  my  office  recently  a  case  of  tuberculosis,  for  example, 
showed  slight  modification  of  symptoms  under  Rape  seed  protein 
(No.  42),  but  responded  promptly  when  a  shift  was  made  to 
Alfalfa  protein  (No.  60).  Such  individual  idiosyncrasies  are  to 
be  expected,  in  the  light  of  our  knowledge  of  varying  suscepti- 
bility to  the  proteins  of  therapeutic  serums,  and  should  always 
be  looked  for  when  a  case  fails  to  respond  to  initial  Proteal  treat- 
ment. No  conclusion  should  be  drawn,  however,  until  after  the 
administration  of  at  least  eight  or  ten  doses. 

It  should  be  borne  in  mind,  also,  that  gradual  and  cumulative 
improvement,  rather  than  sudden  and  spectacular  changes,  may 
be  expected  in  the  treatment  of  such  chronic  and  intractable  con- 
ditions as  psoriasis  and  rheumatoid  arthritis,  even  in  the  most 
favorable  cases. 

The  Proteal  response  is  totally  different  from  the  specific  re- 
sponse of  the  therapeutic  serums  and  vaccines.  Proteals  are  not 
Serums  or  Vaccines.  Each  of  these  words  is  a  generic  term, 
having  a  restricted  meaning,  and  the  words  cannot  properly  be 
used  interchangeably.  By  definition,  a  Proteal  is  a  solution  of 
non-specific  vegetable  proteins.  Serums  are  specific  agents  with 
an  animal  blood  serum  for  the  excipient.  Vaccines,  in  the  mod- 
ern interpretation,  are  specific  bacterial  cultures  containing  the 
dead  bodies  of  bacteria  and  their  toxins. 

Serums  and  vaccines  necessarily  contain  proteins,  and  no  doubt 
they  have  a  non-specific  action  along  with  the  desired  specific 
action.  To  a  limited  extent  they  have  been  used  non-specifically 
(typhoid  vaccine,  for  example,  in  the  treatment  of  arthritis),  but 
such  use  seems  to  me  unwarranted  unless  it  shall  appear  that, 
when  thus  used,  they  have  therapeutic  advantages  over  the  non- 
specific and  non-toxic  vegetable  proteins  (Proteals),  which  lack 
their  toxicity. 

The  vaccines  in  particular,  whatever  their  value  in  this  con- 
nection, cannot  be  expected  to  duplicate  the  Proteal  response,  be- 
cause their  type  of  protein  (bacterial)  is  different  from  that  of 
the  higher  vegetables.  As  illustrating  a  typical  difference  in  re- 
sponse, the  vaccines  invoke  a  polynucleosis,  whereas  a  typical 


20  FOREWORD 

feature  of  the  Proteal  response  is  a  mononucleosis,  and  in  par- 
ticular a  large  monocytosis. 

A  pronounced  anaphylactic  reaction  has  not  been  observed  in 
the  use  of  the  Proteals  prepared  by  the  newer  method.  The  rea- 
son may  be  that  the  proteins  in  the  Proteals  as  now  prepared 
are  partially  hydrolyzed,  appearing  as  proteoses,  and  perhaps  in 
small  part  as  peptones.  The  earlier  Proteals,  comprising  saline 
and  alcoholic  extracts,  contained  the  unbroken  protein  molecule, 
and  their  use  in  repeated  and  maximum  dosage  was  attended 
with  more  or  less  marked  anaphylactic  reactions.  Indeed,  it  was 
my  custom  to  force  the  dosage  until  a  marked  systemic  reaction 
was  produced.  The  absence  of  this  reaction  makes  the  newer 
Proteals  far  pleasanter  to  administer,  and  far  more  acceptable  to 
the  patient,  but  leaves  us  without  a  clinical  guide  to  maximum 
dosage  in  intractable  cases. 

It  may  fairly  be  said  that  no  one  at  present  knows  what  is  the 
maximum  permissible  dose  with  any  Proteal.  Even  with  the 
old  form  of  Proteal,  containing  the  unbroken  protein  molecule, 
the  dose  was  sometimes  advanced  (gradually)  to  forty,  fifty, 
sixty,  and  even  to  ninety  minims;  and,  although  a  severe  sys- 
temic reaction  was  expected  and  even  desired,  no  untoward  result 
was  ever  observed.  I  have  repeatedly  given  to  guinea  pigs  day 
after  day  doses  of  proteins  that,  weight  for  weight,  were  equiva- 
lent to  fifty  or  one  hundred  times  the  maximum  dose  adminis- 
tered therapeutically ;  and  the  animals  thrive  under  the  experi- 
ment. 

Notwithstanding  the  relative  non-toxicity  of  the  Proteals,  I 
regard  it  as  desirable  to  administer  the  smallest  doses  that  will 
produce  results.  If  a  dosage  of  six  or  eight  minims  will  keep 
the  blood  conditions  as  I  like  to  see  them,  with  corresponding 
clinical  improvement,  I  hold  to  such  dosage.  If  it  is  necessary 
to  go  to  a  dosage  of  fifteen  or  twenty  minims,  there  should  be 
no  hesitancy  in  doing  so,  but  beyond  this  it  is  usually  better  to 
shorten  the  interval  between  administrations  rather  than  to  give 
inordinate  single  doses.  These  are  matters,  however,  regarding 
which  individual  cases  differ,  as  do  also  the  preferences  of  dif- 
ferent physicians.  The  experienced  practitioner,  guided  by  per- 
sonal observations,  will  develop  his  own  technique  in  the  use 
of  the  Proteals  as  with  other  lines  of  treatment. 

DEVELOPMENT  OF  THE  PROTEAL  METHOD 

The  theory  of  action  of  Proteals  and  other  non-specific  pro- 
teins, which  originated  .with  the  present  writer  (so  far  as  I  am 
aware,  no  other  has  been  suggested),  is  based  on  my  inter- 
pretation of  the  mechanism  of  immunization  as  first  published 


FOREWORD  21 

in  American  Medicine  for  October  and  November,  1914,  under 
title  of  the  Proteomorphic  Theory.  I  made  the  first  specific  ther- 
apeutic application  of  the  theory  in  detail  to  the  treatment  of  a 
particular  malady,  with  the  explicit  suggestion  that  the  non- 
specific proteins  would  be  applicable  in  combating  all  types  of 
protein  toxaemias,  including  bacterial  diseases,  in  the  New  York 
Medical  Journal  of  October  2,  1915.  A  more  elaborate  explica- 
tion was  given,  with  detailed  study  of  the  blood  modifications 
attending  the  use  of  the  Proteals,  in  a  Monograph  of  126  pages 
bearing  the  title  The  Proteal  Treatment  of  Cancer  and  Allied 
Conditions,  issued  December  1,  1916.  The  name  Proteal  was 
first  introduced  (together  with  the  name  Proteantigen  as  a  fam- 
ily name  for  all  proteins  used  as  antigens,  including  Serums  and 
Vaccines  as  well  as  Proteals),  and  the  principle  that  a  single 
protein  or  combination  of  proteins  must  not  be  depended  on  to 
secure  optimum  results  in  the  majority  of  cases  was  first  pub- 
licly enunciated,  in  this  Monograph,  which  bore  the  sub-title  A 
Practical  Study  of  a  New  Therapeutic  Principle  as  Interpreted 
in  the  Light  of  the  Proteomorphic  Theory. 

The  practical  results  of  Proteal  therapy  in  my  own  hands 
and  in  the  hands  of  several  hundred  associated  physicians  have 
been  of  a  character  calculated  to  arouse  enthusiasm.  I  made  a 
statistical  analysis  of  766  cases,  treated  by  152  physicians,  in  a 
preliminary  report  published  in  the  New  York  Medical  Journal 
of  November  13,  1915.  A  considerable  body  of  new  evidence 
was  available  when  my  Monograph  above  cited  was  published  a 
little  over  a  year  later,  but  this  work  was  largely  devoted  to  the 
theory  of  Proteal  action,  with  especial  reference  to  the  modi- 
fication of  blood  conditions,  to  which  I  had  devoted  assiduous 
attention,  believing  that  to  be  the  crux  of  the  entire  matter. 

During  the  summer  of  1917,  in  the  course  of  a  long  lecture 
tour  in  the  West,  I  delivered  about  one  hundred  addresses  on 
Proteal  Therapy  before  gatherings  of  medical  men,  including  sev- 
eral County  Medical  Societies.  The  interest  aroused  is  evidenced 
in  the  subsequent  use  of  the  Proteals  by  a  large  number  of  phy- 
sicians who  heard  these  addresses.  The  co-operation  of  these 
practitioners  has  been  a  valuable  asset  in  further  tending  to  es- 
tablish the  applications  of  the  Proteals  in  a  variety  of  maladies 
with  which  previous  experience  had  been  limited — including 
asthma  and  tuberculosis.  The  joint  experience  of  this  group  of 
physicians  and  of  others  previously  interested  has  served  to  for- 
tify and  extend  my  personal  observations. 

OTHER  NON-SPECIFIC  PROTEINS 

It  should  be  clearly  understood,  however,  that,  whereas  I  make 
constant  specific  reference  to  the  Proteals,  and  tell  of  the  defi- 


22  FOREWORD 

nite  therapeutic  advantages  attained  with  their  aid,  there  is  no 
contention,  explicit  or  implied,  that  the  particular  proteins  thus 
used  have  any  specific  advantages  over  other  types  of  proteins, 
of  animal  or  vegetable  origin,  that  may  ultimately  be  introduced. 
New  types  of  proteins,  and  new  methods  of  extraction,  are  con- 
stantly being  sought  in  my  laboratory,  and  will  presently  be 
sought  in  numberless  other  laboratories,  if  I  mistake  not,  as  a 
result  of  the  publication  of  the  present  book.  It  is  easily  within 
the  possibilities  that  proteins  far  more  desirable  than  any  hith- 
erto used  may  presently  be  made  available.  But  that  is  a  mat- 
ter of  mere  detail.  The  thing  of  importance  is  that  the  principle 
of  protein  response  has  been — so  I  believe — conclusively  demon- 
strated, and  that  simple  extracts  of  the  proteins  of  alfalfa  seed, 
millet  seed,  rape  seed,  hemp  seed,  clover  seed,  cotton  seed,  and 
the  like  furnish  the  therapeutist  with  new  and  effective  weapons 
in  combating  many  prevalent  maladies  associated  with  disturb- 
ances of  metabolism  and  the  invasion  of  foreign  proteins — mal- 
adies that,  in  the  aggregate,  take  toll  of  hundreds  of  thousands 
of  lives  in  the  United  States  alone  each  year,  and  mar  the  health 
of  uncounted  millions. 

SCIENTIFIC  MEDICINE  VERSUS  EMPIRICISM 

The  physician  who  would  handle  these  new  therapeutic  agents 
effectively  must  have  a  clear  understanding  of  the  principles  that 
underlie  their  therapeutic  action.  To  that  end  it  is  essential 
to  gain  a  full  knowledge  of  the  important  bearings  of  the  Pro- 
teomorphic  Theory.  I  would  urge  the  professional  reader  who 
wishes  to  gain  a  really  comprehensive  grasp  of  the  foundations 
of  Non-specific  Protein  Therapy  in  general  and  of  Proteal  Ther- 
apy in  particular  to  follow  the  chapters  of  this  book  sequentially, 
even  though  he  should  find  some  of  them  repellent  because  of 
their  technicality. 

When  he  has  done  so,  it  will  be  clear  to  him  that  Proteal 
Therapy  differs  from  routine  medical  practice  in  that  it  may  with 
propriety  be  said  to  be  an  applied  science.  Within  the  wide 
bounds  of  the  application  of  the  Non-specific  Protein  method, 
medicine  ceases  to  be  a  merely  empirical  art.  No  man  knows 
how  or  why  morphine  or  strychnine  or  atropine  or  digitaline  pro- 
duce their  perennially  observed  and  perfectly  recognized  effects. 
With  the  Proteals,  the  case  is  different.  We  know  how  and  why 
they  operate.  The  physiological  response  that  they  evoke  may 
be  observed  and  demonstrated  under  the  microscope.  The  dosage 
may  be  gauged  in  the  same  way.  In  administering  them,  we  are 
no  longer  groping  in  the  dark,  along  an  empirical  pathway.  We 
are  practising  scientific  medicine. 


FOREWORD  23 

To  be  sure,  our  knowledge  of  this  new  science  of  Non-specific 
Protein  Therapy  is  only  in  its  rudiments.  Prior  to  the  appear- 
ance of  my  paper  of  October,  1914,  the  principles  upon  which 
it  is  based  had  not  been  explicitly  formulated.  Prior  to  October 
2,  1915,  no  comprehensive  statement  of  the  therapeutic  possibili- 
ties of  the  method  had  been  published.  Prior  to  July,  1916,  no 
conclusive  demonstration  of  the  Protein  principle,  as  such,  had 
been  made.  And  the  first  elaborate  formulation  of  the  micro- 
scopical evidence  in  support  of  the  earlier  inferences  was  pub- 
lished as  recently  as  December  1,  1916.  Meantime  a  collocation 
of  the  entire  evidence  available  up  to  date,  reproducing  in  full 
the  original  formulation  of  the  Proteomorphic  Theory  itself, 
with  sundry  amplifications,  and  detailing  the  applications  of  the 
method  throughout  the  wide  domain  of  disturbed  protein  meta- 
bolism, is  given  for  the  first  time  in  the  present  work,  in  com- 
bination with  the  second  edition  of  the  Monograph  on  The  Pro- 
teal  Treatment  of  Cancer  and  Allied  Conditions,  announced  for 
issue  early  in  April,  1918. 

Notwithstanding  the  newness  of  the  subject,  however,  Proteal 
therapy  has  passed  far  beyond  the  experimental  stage.  Much 
remains  to  be  learned,  of  course,  but  much  that  is  definite  and 
tangible  is  already  precisely  known.  I  have  personally  adminis- 
tered many  hundreds  of  doses  of  the  various  Proteals  to  patients 
suffering  from  a  wide  range  of  maladies,  from  simple  asthenias 
and  anaemias  to  pernicious  anaemia,  intestinal  toxaemia,  lymphatic 
leukaemia,  arteriosclerosis,  rheumatoid  arthritis,  goitre,  cancer, 
and  tuberculosis.  My  direct,  personal  office  and  bedside  observa- 
tion of  patients  under  Proteal  treatment  comprises  not  far  from 
five  hundred  cases.  I  have  been  professionally  consulted  by 
fellow-physicians  and  have  advised  with  reference  to  the  Pro- 
teal  treatment  of  about  two  thousand  additional  cases.  My  office 
files  contain  more  than  six  thousand  letters  dealing  directly  with 
the  subject,  received  (and  I  may  add,  without  exception,  promptly 
answered)  within  the  past  two  and  a  half  years.  My  original 
blood-examination  records  number  not  far  from  twelve  hundred. 

Meantime  more  than  fourteen  thousand  ampules  of  the  various 
Proteals  have  been  sent  out  from  my  private  laboratory  to  co- 
operating members  of  the  profession  within  the  past  year,  and 
reports  from  these  physicians  give  invaluable  clues  to  the  appli- 
cations and  limitations  of  the  method. 

The  deductions  from  this  substantial  experience,  including  a 
full  elaboration  of  my  hematological  discoveries,  constituting  the 
first  comprehensive  study  of  the  Theory  and  Practice  of  Proteal 
Therapy,  appear  in  the  present  book. 

Here,  and  in  the  Monograph  so  frequently  cited,  I  have  at- 
tempted to  justify  by  evidence  my  belief  that  the  non-specific 


24  FOREWORD 

protein  response  constitutes  one  of  the  most  comprehensive  prin- 
ciples known  to  scientific  therapeutics,  and  that  the  Proteals  fur- 
nish the  practitioner  with  new  weapons  of  genuine  value  in 
combating  a  long  list  of  intractable  maladies  of  middle  life  and 
old  age,  including  anaemias,  leukaemias,  toxaemias,  rheumatoid 
conditions,  goitre,  arteriosclerosis,  asthma,  tuberculosis,  psoriasis, 
and  cancer.  The  candid  physician  who  has  not  had  personal 
experience  in  the  use  of  the  Proteals  may  advantageously  reserve 
judgment  regarding  the  possibilities  of  the  method  until  he  has 
reviewed  the  evidence  as  presented  in  these  books. 

With  a  method  so  new  there  is  necessarily  much  still  to  be 
tested.  Some  of  the  open  problems  will  be  discussed  in  the 
succeeding  pages.  But  in  the  main  the  record  here  presented 
deals  with  the  definite  achievements  already  in  hand.  The  work 
is  by  no  means  finished,  but  I  repeat  that  it  has  passed  far  beyond 
the  experimental  stage.  Proteal  therapy  is  to-day  a  verity.  In 
the  hands  of  hundreds  of  practitioners  it  has  proved  its  utility. 
When  the  newly  discovered  physiological  laws  on  which  it  is 
based  are  generally  known  and  recognized,  the  use  of  the  method 
will  become  universal. 

Such,  at  least,  is  the  confident  belief  in  which  this  book — 
the  first  attempt  at  comprehensive  presentation  of  the  Theory 
and  Practice  of  Proteal  Therapy  in  its  wider  relations — is  offered 
to  the  medical  profession. 


THE   PROTEOMORPHIC  THEORY 
AND  THE  NEW  MEDICINE 

CHAPTER  I 

THE  MECHANISM  OF  PROTEIN  HYDROLYSIS  AND 
IMMUNIZATION 

The  main  theses  of  the  Proteomorphic  Theory  are  these :  That 
the  mechanism  which  gives  the  human  organism  partial  or  com- 
plete immunity  against  bacterial  disease  comprises  what  may  be 
called  the  cytogenic  or  haematopoietic  system — including  lym- 
phatics, bone  marrow,  and  spleen — with  its  daughter  cells  the 
white  and  red  blood  corpuscles  as  its  active  agents,  and  with  the 
liver  as  the  excretory  organ  of  the  waste  products  incidental 
to  the  immunizing  process;  and  that  the  same  mechanism  deals 
with  all  foreign  proteins  in  the  parenteral  system;  the  case  of 
the  bacteria  being  only  a  special  case  within  the  general  law  of 
protein  hydrolysis.. 

The  white  corpuscles  are  believed  to  begin  hydrolysis  of  foreign 
protein,  and  the  red  corpuscles  to  complete  the  decompounding 
from  the  polypeptid  stage,  liberating  amino-acids,  and  dealing  also 
with  residual  end  products  of  the  zanthin-uric  acid-urea  series. 
Sundry  antibodies  of  the  general  character  of  enzymes  are  coin- 
cidentally  developed,  their  individual  qualities  being  determined 
in  response  to  the  specific  nature  of  the  invading  protein,  bac- 
terial or  non-bacterial. 

The  theory  assumes  that  the  entire  cellular  system  of  the 
organism — viscera,  muscles,  brain — may  be  considered  as  a  sec- 
ondary apparatus,  standing  as  it  were  in  the  background,  ready 
to  supplement  the  work  of  the  chief  immunizing  agents.  So 
general  an  implication  as  the  latter  may  seem  to  savor  of  the 
nature  of  a  truism ;  but  it  will  appear  that  the  theory  ascribes  a 
specific  and  definite  part  in  the  immunizing  process  to  the  body- 
cells  in  general  and  in  particular,  attempting  to  trace  the  precise 
rationale  of  their  activity.  Equally  specific  is  the  interpretation 
of  the  activities  of  the  leucocytes  and  the  red  blood  corpuscles, 
which  are  posited  as  the  chief  and  controling  mechanism  in  the 
process  of  protein  hydrolysis  in  general  and  immunization  in 
particular. 

It  will  be  well  here  at  the  outset  to  present  a  summary  of  the 
chief  tenets  of  the  theory,  by  way  of  orienting  the  mind  of  the 

25 


26      THE   PROTEOMORPHIC   THEORY   AND  THE   NEW    MEDICINE 

reader,  and  preparing  him  better  to  follow  the  detailed  argu- 
ment to  which  the  ensuing  hundred  pages  or  so  are  devoted. 
The  essentials  of  the  theory,  then,  are  the  following: 

1.  The  chief  immunizing  mechanism  of  the  body  is  the  cyto- 
genic  mechanism,  of  which  the  recognized  members  are  the  bone 
marrow,  the  spleen,  and  the  lymphatic  system.    The  active  agents 
through  which  the  process  of  immunization  is  carried  out  are  the 
leucocytes  and  red  blood  corpuscles  generated  in  the  various 
organs  of  this  system. 

2.  The  prime  function  of  the  leucocyte,  after  it  becomes  a 
freely  moving  cell,  is  to  facilitate  and  complete  protein  cleavage 
or  digestion,  preparing  for  assimilation  (to  the  limit  of  its  ca- 
pacity) all  foreign  proteins  that  enter  the  blood  stream.    In  pur- 
suance of  this  function,  it  is  provided  with  digestive  enzymes, 
and  with  a  mechanism  for  the  production  of  special  types  of  pro- 
teolytes  to  cleave  an  endless  variety  of  protein  molecules,  and 
to  counteract  toxic  proteins  or  enzymes  due  to  bacterial  activities. 

It  is  believed  that,  generally  speaking,  the  eosinophiles  and 
large  monocytes  deal  with  the  protein  molecule  unbroken  or  at 
an  early  stage  of  hydrolysis ;  the  small  lymphocytes  and  polynu- 
clears  with  intermediate  and  later  stages  of  hydrolysis;  their 
functions,  however,  more  or  less  overlapping,  and  their  aggregate 
activities  carrying  the  invading  protein  to  the  polypeptid  stage 
of  decompounding. 

3.  The  red  blood  corpuscle  completes  the  hydrolysis  of  poly- 
peptid and  allied  protein  products  that  find  their  way  into  the 
blood  stream.    It  absorbs  or  counteracts  the  toxic  residual  mole- 
cules that  are  not  completely  hydrolyzed ;  and  it  antagonizes  the 
products  of  bacterial  activity,  producing  antitoxins.     When  ulti- 
mately autolyzed  or  destroyed,  chiefly  in  the  liver,  it  gives  its 
protein  and  enzymes  to  the  blood  stream,  and  its  waste  products 
are  discharged  from  the  body  through  the  bile  duct  and  (in  the 
form  of  uric  acid,  urea,  and  creatinine)   through  the  kidneys. 
The  functions  of  the  red  corpuscles  in  thus  dealing  with  the  end 
products  of  protein  hydrolysis  (reducing  polypeptids  to  ammo- 
acids  and  residual  products)  is  conceived  to  be  of  fundamental 
importance,  as  indispensable  as  the  function  of  carrying  oxygen. 
An  important  specific  feature  includes  the  oxidizing  of  the  purin 
bases  to  form  uric  acid,  and  the  more  or  less  complete  transfor- 
mation of  the  uric  acid  into  urea. 

4.  The  chief  work  of  synthesizing  protein  out  of  amino-acids 
in  the  organism  resides  with  the  mother  cells  of  the  cytogenic 
apparatus — notably  the  bone  marrow  and  the  spleen.     But  the 
cells  of  each  specialized  tissue — muscles,  brain,  glands — can  on 
occasion  synthesize  each  its  own  special  type  of  protein,  utilizing 
the  amino-acid  building  materials.    Each  tissue  can  also,  on  occa- 


MECHANISM   OF  PROTEIN    HYDROLYSIS  AND  IMMUNIZATION      27 

sion,  hydrolyze  nitrogenous  molecules  of  the  polypeptid  order, 
and  give  out  antitoxic  ferments  in  response  to  specific  toxins. 
But  as  a  rule  the  tissues  are  shielded  by  the  red  blood  corpuscles 
from  the  necessity  of  performing  these  functions. 

5.  The  vast  multitudes  of  red  blood  corpuscles,  with  an  aggre- 
gate bulk  of  about  four  pounds  in  the  ordinary  human  body, 
their  substance  having  been  synthesized  by  the  mother  cells  out 
of  amino-acids,  constitute  the  chief  source  of  the  specific  pro- 
teins in  the  blood  stream,  which  proteins  on  being  decompounded 
(possibly  with  the  aid  of  the  lymphocytes  and  polynuclears)  are 
the  prominent  sources  of  bodily  energy. 

6.  Every  cell  that  can  unite  with  a  foreign  proteid  product 
can  produce  an  "antibody"  calculated  to  antagonize  that  prod- 
uct.   The  leucocytes  and  red  blood  corpuscles  are  the  particular 
cells  that  come  most  in  contact  with  such  foreign  bodies,  and 
they  are  therefore  the  chief  source  of  specific  proteolytes  and 
antibodies  directed  against  the  invaders.     The  presence  in  the 
blood  stream  of  these  specific  proteolytes  and  antibodies,  se- 
creted by  the  leucocyte  and  red  cells,  and  to  a  certain  extent  by 
the  body-cells  (backed  up  by  the  presence  of  an  adequate  army 
of  leucocytes  and  red  cells  themselves,  capable  of  producing  more 
of  the  antibodies  under  stimulus  of  invasion),  constitutes  the 
condition  of  immunity. 

7.  Immunization  to  bacterial  disease  is  merely  a  special  case 
of  protein  assimilation.     It  has  in  the  past  been  as  necessary 
to  acquire  immunization  against  the  dietetic  proteins — oyster, 
fish,  egg,  fowl,  milk,  mutton,  pork,  beef — and  against  "benign" 
bacteria  as  against  the  most  virulent  bacteria. 

8.  So-called  harmless  or  benign  bacteria  are  those  that  have 
been  long  with  us,  and  which,  therefore,  the  leucocytic  and  ery- 
throcytic  mechanisms  have  learned  adequately  to  combat  and  con- 
trol.   Virulent  bacteria  are  the  relatively  rare  ones  or  those  that 
have  visited  us  infrequently.    A  relatively  benign  bacterium  may 
become  malignant,  however,  through  changed  conditions  leading 
it  to  ingest  unwonted  types  of  protein ;  or  through  developing 
exceptional  vigor;  or  through  invading  the  system  in  excessive 
numbers. 

9.  Protein  anaphylaxis  of  any  type  (including  "serum  disease") 
is  merely  a  special  case  of  protein  intoxication,  strictly  homolo- 
gous with  protein  poisoning  from  the  toxins  of  virulent  bacteria. 
It  results  when  a  general  proteolytic  (leucocytic)  enzyme  is  pres- 
ent in  sufficient  quantity  to  hydrolyze  the  foreign  protein  partly, 
while  the  red-cell  mechanism  is  temporarily  exhausted,  so  that 
cleavage  cannot  be  completed,  and  the  tissue  cells — in  particular 
the  brain  cells — are  attacked.      Protein   anaphylaxis   is   strictly 
homologous  with  protein  immunization.     They  are  different  as- 


28      THE   PROTEOMORPHIC   THEORY  AND  THE   NEW    MEDICINE 

pects  of  the  same  subject  corresponding  respectively  to  the  "pas- 
sive phase"  and  the  "active  phase"  of  Wright's  "opsonic  index." 

10.  The  activities  of  the  cytogenic  system,  leading  to  an  in- 
crease in  the  number  of  blood  corpuscles  and  a  stimulus  to  the 
activities  of  the  individual  corpuscles ;  and  through  these  to  com- 
pleted protein  assimilation  and  immunization,  are  governed  in 
part  by  hormonic  stimuli ;  the  internal  secretions  actively  engaged 
including  those  of  the  adreno-thyroid  system  and  secretin  from 
the  duodenum. 

11.  The  cytogenic  system    (including  the  bone  marrow,  the 
spleen,  and  the  lymphatic  glands)  is  a  highly  important  member 
of  the  endocrinous  system ;  the  detached  blood  corpuscles  are 
to  be  regarded  as  still  a  part  of  that  system;  and  the  study  of 
the  system  as  a  whole  offers  a  fruitful  field  for  discovery  of 
new  methods  in  immunization  and  the  treatment  of  infectious 
diseases. 

The  hypothesis  of  immunization  thus  summarized,  being  based 
on  the  activities  of  the  cells,  might  appropriately  enough  be  termed 
the  Cytoclastic  theory,  were  it  not  that  the  term  seems  too 
general  and  not  sufficiently  explicative.  It  might  be  termed  the 
Corpuscular  theory,  in  token  of  the  role  ascribed  to  both  types 
of  blood  corpuscles,  were  it  not  that  physical  science  has  already 
usurped  that  term.  To  call  it  the  Leucocytic  theory  would  be 
quite  inadequate,  as  it  would  credit  only  one  member  of  the! 
triumvirate,  and  would,  moreover,  signalize  the  least  original  por- 
tion of  the  theory  itself.  The  term  Erythrocytic  theory  would 
have  somewhat  greater  propriety,  as  pointing  out  what  is  con- 
ceived to  be  the  most  important  single  agent  in  the  immunizing 
process,  and  also  as  signalizing  the  most  novel  feature  of  the 
theory.  But  this  term  also  is  condemned  by  its  obvious  inade- 
quacy. 

On  the  whole,  the  term  Proteomorphic  theory  is  the  most  com- 
prehensive and  explicative  one  that  suggests  itself;  inasmuch 
as  the  theory  at  all  stages,  and  in  its  widest  implications,  has  to 
do  with  the  metamorphoses  (mainly  hydrolytic)  of  protein 
compounds. 

It  was  through  study  of  proteoclasis,  mainly — in  connection  of 
course  with  the  fairly  wide  survey  of  a  good  many  allied  fields — 
that  the  theory  itself  was  elaborated.  But  for  the  data  supplied 
by  study  of  proteolytic  activities,  in  connection  with  the  meta- 
bolic processes  of  normal  and  abnormal  digestion  and  assimila- 
tion, the  theory  could  not  have  been  conceived.  So  the  word 
proteomorphic  may  be  used  to  designate  it  with  peculiar  propriety. 

It  will  appear  in  the  course  of  the  following  exposition  that 
a  good  many  other  laboratory  and  clinical  observations,  hitherto 


MECHANISM    OF   PROTEIN    HYDROLYSIS   AND    IMMUNIZATION      29 

utterly  obscure  or  but  vaguely  interpreted,  find  clear  and  tangible 
explanation  when  viewed  in  the  light  of  the  proteomorphic  theory. 

It  will  be  shown  that  the  precise  role  of  the  leucocyte  on  one 
hand  and  the  side-chain  mechanism  on  the  other  are  inter- 
preted from  a  new  point  of  view ;  that  the  red  blood  corpuscle 
is  conceived  to  enter  into  the  scheme  of  immunization  as  a  mas- 
terful and  dominating  force,  with  all-important  activities  never 
hitherto  ascribed  to  it;  and  that,  as  a  whole,  the  scheme  of 
immunization  here  presented  has — if  its  tenets  be  accepted — a 
measure  of  comprehensiveness  in  the  interpretation  of  the  find- 
ings of  physiologist,  bacteriologist,  and  clinical  pathologist  that 
could  not  well  be  claimed  for  any  theory  of  immunization  here- 
tofore submitted.  More  than  that,  the  theory  has  pointed  the 
way  to  a  new  field  of  therapeutics,  already  demonstrated  to  be 
large  and  important,  the  full  limitations  of  which  will  not  be 
determined  for  a  long  time  to  come — the  field  of  Nonspecific 
Protein  Therapy. 

Before  going  on  to  the  practical  therapeutic  developments  of 
the  idea,  it  is  desirable  to  present  the  evidence  for  the  Proteo- 
morphic theory  itself,  drawn  from  various  fields  of  biology  and 
pathology. 

In  collating  the  evidence  it  will  be  necessary  to  summarize  the 
results  of  experiments  and  observations  gleaned  from  many  dif- 
ferent sources,  some  of  which  must  necessarily  be  familiar  to 
all  medical  readers,  and  all  of  which  will  perhaps  be  familiar 
to  a  few.  This  is  unavoidable  if  the  evidence  in  its  totality  is 
to  be  made  generally  comprehensible. 

It  will  appear  as  we  proceed  that  much  of  this  evidence  is 
indirect  or  circumstantial ;  yet  in  the  aggregate,  I  believe,  it 
establishes  a  strong  presumption  in  favor  of  the  validity  of  the 
theory  advanced.  And  if  the  theory  is  accepted,  certain  very 
definite  and  rather  important  inferences  as  to  practical  thera- 
peutic applications  follow  as  matters  of  course.  The  study  of 
the  blood  corpuscles  assumes  new  interest  and  importance  for 
the  practical  therapeutist.  The  genesis  of  anaemias  of  various 
types,  including  pernicious  anaemia,  is  more  clearly  explained 
than  ever  before,  on  the  assumption  that  the  destruction  of  red 
corpuscles  is  due  to  excessive  demands  put  upon  them  by  the 
surcharging  of  the  blood  with  protein  end  products.  The  differ- 
ential count  of  the  leucocytes  other  than  the  polynuclears  becomes 
for  the  first  time  intelligible  and  susceptible  of  interpretation. 

Specifically,  it  would  appear  that  a  monocytosis  is  as  char- 
acteristic and  as  pathognomonic  an  evidence  of  protein  intoxi- 
cation as  a  polynucleosis  is  of  bacterial  infection;  and  that  the 
artificial  stimulation  of  a  large  monocytosis  (as  by  hypodermic 
introduction  of  foreign  proteins)  is  a  therapeutic  expedient  sus- 


30      THE    PROTEOMORPHIC   THEORY   AND   THE    NEW    MEDICINE 

ceptible  of  application  in  dealing  with  a  wide  range  of  maladies 
associated  with  disturbances  of  protein  metabolism. 

All  this  will  be  taken  up  in  detail  as  we  proceed.  Our  first 
concern,  however,  is  with  the  previously  established  facts  as  to 
the  systemic  response  to  the  invasions  of  proteins  chiefly  of  the 
bacterial  order. 

FACTS  AND  THEORIES  OF  IMMUNITY 

For  generations  physicians  have  been  aware  that  an  attack 
of  a  contagious  disease  tends  to  give  the  subject  immunity  against 
further  attacks  of  that  disease.  The  discovery  of  Jenner  gave 
an  inkling  of  the  possibilities  of  preventing  disease  by  inocula- 
tion, but  this  purely  empirical  procedure  did  not  lead  directly 
to  any  extension  of  the  method.  It  was  only  after  the  bac- 
teriologist had  discovered  the  tangible  cause  of  disease  that  a 
way  was  found  to  produce  artificial  immunization. 

In  1887  Pasteur  startled  the  world  by  demonstrating  that  a 
virulent  bacillus  could  be  attentuated  as  to  its  virulence  by  cul- 
tivation in  an  artificial  medium,  and  that  an  animal  inoculated 
with  the  virus  thus  produced  was  given  immunity  from  the  dis- 
ease, even  though  subsequently  inoculated  with  virulent  germs. 
In  1890  Behring  discovered  that  the  blood  of  an  animal  thus 
immunized  has  power  to  transmit  the  immunizing  principle,  what- 
ever it  might  be,  to  another  animal  if  the  blood  serum  of  the 
immune  animal  is  injected  hypodermatically  or  intravenously. 
The  diphtheria  antitoxin  thus  developed  by  Behring,  and  a  tet- 
anus antitoxin  discovered  by  Behring  and  Kitasato,  were  soon 
added  to  the  armamentarium  of  the  physician. 

At  about  the  same  time,  Ehrlich  conducted  his  classical  series 
of  experiments  with  vegetable  poisons,  notably  ricin  and  abrin 
(the  toxic  principles,  respectively,  of  the  castor-oil  bean  and  the 
seed  of  jequirity).  He  found  that  an  animal  inoculated  with 
either  of  these  proteid  substances  developed  an  immunizing  prin- 
ciple which,  when  mixed  with  the  poison  itself  in  vitro  neutralized 
the  poison.  It  was  necessary  to  make  the  admixture  in  certain 
proportions,  thus  showing  the  chemical  nature  of  the  reaction. 
Ehrlich  thought  of  the  phenomenon  in  chemical  terms ;  yet,  for 
the  purpose  of  bringing  the  matter  vividly  to  the  attention  of  the 
profession,  he  devised  a  mechanical  scheme  in  explanation  of  the 
phenomenon  of  immunity  which  soon  found  almost  universal 
acceptance,  and  which  is  often  incorrectly  thought  of  as  suggest- 
ing something  quite  different  from  chemical  combinations. 

Ehrlich's  tangible  diagrams  showing  his  "receptors"  of  the  first, 
second,  and  third  order ;  his  haptophores  and  toxophores ;  his 
zymorphous  and  complementophile  groups  of  the  complex — all 


MECHANISM   OF  PROTEIN    HYDROLYSIS  AND   IMMUNIZATION      31 

depicted  as  tangible  structures,  some  of  them  resembling  hungry 
polywogs  biting  eagerly  at  inviting  bits  of  protruding  protoplasm 
of  just  the  right  size  to  make  a  mouthful — proved  altogether 
alluring.  A  glance  at  such  a  diagram  enables  one  to  form  a  clear 
mental  picture  of  the  relations  of  receptive  cells  and  complement 
and  immune  bodies  in  happy  disregard  of  all  possible  chemical 
complexities. 

In  due  course  numerous  workers  proved  the  universality  of 
application  of  the  principles  of  the  formation  of  the  antibodies 
through  the  introduction  of  toxic  agents  into  the  organism.  We 
learned  of  antitoxins,  anti ferments,  cytotoxins,  agglutinins,  pre- 
cipitins,  and  opsonins  in  the  normal  blood  serum  or  developed  spe- 
cifically in  response  to  the  invasion  of  toxins ;  then  it  appeared 
that  there  may  be  anticytotoxins,  anti  ferments,  etc.;  in  bewilder- 
ing profusion.  And  it  was  at  least  suggested  that  were  our 
means  of  investigations  sufficiently  delicate  we  should  find  anti- 
antibodies  in  unending  series,  each  new  antidote  becoming  in 
turn  a  toxin  and  requiring  an  antidote ;  and  the  orgainc  labora- 
tory proving  quite  capable  of  developing  series  of  such  responsive 
mechanism  ad  infinitum. 

To  add  to  the  confusion,  different  workers  gave  different  names 
to  the  substances  revealed  in  the  course  of  their  investigations ; 
and  in  many  cases  they  were  talking  of  the  same  thing  in  terms 
of  a  different  nomenclature.  Thus  the  ferment  that  Ehrlich  calls 
addiment  was  named  by  others  alexine,  by  still  others  cytase 
and  yet  again  complement — the  last  name  being  the  one  ulti- 
mately adopted  by  most  authorities. 

In  the  same  way  the  immune  bodies  came  to  be  known  as 
amboceptor,  copula,  desmon,  hilfskorper,  zwischenkorper,  fixa- 
teur  substance,  sensibilisatrice,  etc.  And  it  became  a  matter 
for  dispute  as  to  whether  agglutinins,  precipitins,  and  opsonins 
are  identical  one  with  another,  and  also  as  to  the  relations  that 
these  substances — recognized  only  by  their  effects — bear  to  the 
various  hemolysins,  bactericides,  and  bacteriolysins. 

Out  of  the  confusion,  however,  emerged  pretty  clearly  the 
conception  that  there  are  two  types  of  so-called  bodies  or  chem- 
icals involved  in  the  immunizing  process.  One  of  these  is  a 
ferment-like  substance  which  is  thermolabile,  its  action  being 
prevented  by  heating  to  a  temperature  of  about  sixty  degrees 
centigrade ;  this  substance  being  conveniently  referred  to  as  the 
complement.  Joined  with  the  complement  in  the  immunizing 
process  is  a  thermostable  substance  which  may  be  comprehen- 
sively termed  the  immune  body  which  apparently  includes  agglu- 
tinins, opsonins,  and  bacteriolysins  (whether  or  not  these  are 
identical).  The  thermolabile  complement  is  non-specific,  in  the 
sense  that  the  same  complement  may  unite  with  many  types  of 


32      THE    PROTEOMORPHIC   THEORY   AND   THE    NEW    MEDICINE 

immune  bodies.  But  the  thermostable  immune  body  is  specific, 
in  the  sense  that  it  is  evoked  in  response  to  a  specific  protein  or 
toxin  (called  an  antigen),  and  is  antidotal  to  the  particular  antigen 
that  evokes  it  alone.  A  bacteriolysin,  for  example,  evoked  in 
response  to  the  typhoid  bacillus  will  not  destroy  the  tetanus 
bacillus. 

The  validity  of  the  conceptions  associated  with  these  terms  is 
not  to  be  questioned.  Multitudes  of  experiments  have  shown 
that  the  terms  "complement"  and  "immune  body,"  and  the  ideas 
associated  with  them,  are  compatible  with  observable  phenomena 
of  the  bacteriological  world.  The  assumption  that  active  comple- 
ment must  be  present  in  order  that  immune  body  may  be  linked 
with  the  toxic  agent  to  neutralize  it,  finds  support  in  such  prac- 
tical work  as  Widal's  agglutinizing  test  for  typhoid  fever  and 
Wasserman's  fixation-of-the-complement  test  for  the  diagnosis  of 
syphilis.  The  conception  that  the  toxic  molecule  has  a  "hapto- 
phore"  group  and  a  "toxophore"  group  and  that  the  cell  has 
receptors  of  a  typical  mechanical  structure  on  which  the  hapto- 
phores  adjust  themselves  is  so  tangible  that  it  makes  immediate 
and  strange  appeal  to  the  imagination,  or,  better  stated,  it  makes 
it  unnecessary  to  call  the  imagination  into  play  at  all,  the  dia- 
grams supplying  its  place. 

I  chanced  to  be  living  in  London  in  1900,  and  I  had  the  pleas- 
ure of  hearing  Ehrlich  deliver  his  Croonion  Lecture  before  The 
Royal  Society,  expositing  his  epoch-making  theory.  Subse- 
quently I  visited  Ehrlich  at  the  famous  Institute  at  Frankfort, 
and  talked  with  him  about  newer  aspects  of  the  great  problem 
of  immunization,  with  particular  reference  to  the  possibilities  of 
specific  therapy,  which  were  then  holding  his  attention  in  con- 
nection with  the  development  of  salversan  and  the  attempted 
selenium  cancer  specific.  My  own  original  investigations  have 
led  to  developments  rather  along  the  line  of  extension  of  an- 
other field  in  which  Ehrlich  was  a  pioneer,  namely  the  study  of 
the  tangible  activities  of  the  corpuscles;  but  like  all  workers  in 
allied  fields  I  have  found  aid  and  stimulation  in  the  graphic  de- 
signs with  which  Ehrlich  attempted  to  make  his  conceptions 
intelligible. 

Unquestionably  these  diagrams  have  proved  very  useful,  and 
the  entire  mechanical  conception  has  done  much  to  promul- 
gate widely  a  more  or  less  comprehensible  conception  of  the 
mechanism  of  immunity.  But  it  is  at  least  an  open  question  as 
to  whether  these  diagrams  have  not  now  served  their  purpose, 
and  whether  it  may  not  be  well  to  revert  to  a  somewhat  differ- 
ent point  of  view,  and,  ultimately,  to  adopt  a  terminology  more 
in  keeping  with  the  expression  of  chemical  ideas  in  general.  For 
of  course  it  would  be  absurd  to  imagine  that  the  mechanical  dia- 


MECHANISM   OF  PROTEIN    HYDROLYSIS  AND   IMMUNIZATION      33 

grams  have  any  representation  in  the  world  of  fact.  They  are 
figments  of  the  imagination,  and  may  serve  some  such  useful 
purpose  as  picture  blocks  serve  in  teaching  a  child  the  alphabet. 
But  as  the  time  comes  when  the  child  puts  aside  the  blocks  and 
takes  in  hand  the  pen,  so  pathologists  must  ultimately  lay  aside 
the  crude  mechanism  of  haptophores  and  amboceptors  and  learn 
to  deal  with  the  phenomena  of  immunity  in  terms  of  the  protein 
molecule  and  the  chemical  atom. 

PROTEIN  METABOLISM 

To  be  sure  the  chemistry  of  the  protein  molecule  is  by  no 
means  as  clearly  understood  as  might  be  desired,  even  by  spe- 
cialists in  biochemistry.  But  the  researches  of  many  workers 
in  recent  years  have  resulted  in  tearing  the  molecule  apart  in 
the  laboratory,  and  in  revealing  the  major  part  of  its  primary 
constituents.  We  are  now  gaining  an  inkling  as  to  what  really 
happens  when  proteid  foods  are  taken  into  the  digestive  tracts 
and  subjected  to  the  digestive  ferments.  And  we  are  beginning 
to  realize  that  the  subject  has  supreme  importance  from  the 
standpoint  of  the  student  of  infectious  diseases,  for  the  simple 
but  all-sufficient  reason  that  the  microbic  agents  that  cause  these 
diseases  are  themselves  protoplasmic  bodies — that  is  to  say,  com- 
pounds of  protein.  I  shall  argue  presently  that  the  bacterial 
proteins  are  of  a  relatively  unevolved  type,  comparable  perhaps 
in  complexity  to  peptones  rather  than  to  full-sized  molecules  of 
the  proteins  of  higher  plants  and  of  animals;  but  in  any  event 
the  difference  is  one  of  degree  only.  The  bacterial  substance, 
within  its  lipoid  membrane,  is  a  nitrogenous  or  proteid  body. 

When  we  reflect  that  there  are  always  myriads  of  these  pro- 
teid bodies  in  the  digestive  tract;  and  that  legions  of  them  on 
occasion  find  their  way  into  the  vascular  system,  and  are  there 
digested,  the  pertinence  of  the  topic,  in  relation  to  protein  meta- 
bolism, becomes  evident. 

And  from  the  present  standpoint  the  chief  interest  centers 
on  the  fact  that  there  is  in  the  human  body  one  set  of  cells  and 
one  only  that  has  been  demonstrated  to  be  able  to  digest  and 
metamorphose  the  bacterial  proteins  when  once  they  have  invaded 
the  blood  stream — namely  the  leucocytes.  What  the  ferments 
of  the  digestive  tract  accomplish  in  the  case  of  the  food  pro- 
teins, is  accomplished  by  ferments  of  the  leucocyte  in  the  case 
of  the  bacterial  proteins  with  which  it  comes  in  contact. 

I  shall  suggest  that  the  function  of  the  leucocyte  in  this  capac- 
ity is  far  more  general,  having  to  do  with  the  metamorphosis 
of  many  types  of  protein  in  addition  to  those  that  come  with  the 
bacteria;  but  for  the  moment  it  suffices  to  call  attention  to  the 


34      THE   PROTEOMORPHIC  THEORY   AND  THE    NEW    MEDICINE        . 

fact  that  the  leucocyte  is  demonstrated  to  be  able  to  deal  with 
complex  proteins,  inasmuch  as  it  is  observed  to  engulf  and  assim- 
ilate protein-bearing  bacteria  in  toto. 

That  the  leucocyte  actually  performs  this  feat,  was  first  dem- 
onstrated by  MetchnikofT,  and  has  been  re-demonstrated  thou- 
sands of  times  over  in  recent  years,  notably  by  the  students  of 
vaccine  therapy.  But  the  significance  of  this  phenomenon,  in 
its  broader  aspects,  although  at  least  partially  conceived  by 
Metchnikoff  himself,  was  largely  overlooked  by  his  successors. 

It  must  not  be  understood,  however,  that  the  capacities  of  the 
leucocyte  as  a  proteoclastic  agent  have  been  altogether  ignored 
by  recent  workers.  On  the  contrary,  it  is  probable  that  some 
of  the  physiological  chemists  have  ascribed  to  the  leucocyte  in 
this  connection  a  larger  measure  of  activity  than  it  actually  exer- 
cises. Thus  Hofmeister,  stimulated  no  doubt  by  the  discoveries 
of  MetchnikofT,  was  led  to  ascribe  to  the  leucocyte  the  all- 
important  function  of  taking  up  the  peptone  believed  (errone- 
ously) to  be  absorbed  through  the  intestinal  wall,  and  converting 
it  into  protein  either  directly  or  with  the  aid  of  the  adenoid 
tissues,  thus  making  it  available  for  assimilation  by  the  body  cells 
in  general. 

The  peptone  molecule,  it  will  be  recalled,  is  a  cleavage  product 
developed  from  the  original  protein  molecule  of  a  food  protein 
hydrolyzed  through  the  agency  of  the  digestive  ferments  of  stom- 
ach, upper  intestine,  and  pancreas.  The  molecule  of  peptone  has 
a  molecular  weight  of  only  about  four  hundred,  being  therefore 
about  one-fortieth  the  size  of  its  parental  protein  molecule.  To 
conceive  that  the  leucocyte  habitually  takes  this  relatively  small 
molecule  as  its  building  stone  and  elaborates  the  complex  pro- 
tein molecule  the  molecular  weight  of  which  runs  high  into  the 
thousands — and  does  this  in  case  of  all  the  protein  that  the 
body  utilizes — is  to  make  an  assumption  that  at  the  least  seems 
amazing. 

Yet  Hofmeister  thought  that  he  found  justification  for  this 
assumption  in  the  fact  that  there  is  a  marked  postprandial  leuco- 
cytosis.  If  the  leucocyte  does  not  perform  the  function  of  com- 
pleting digestion  of  the  food  and  facilitating  assimilation,  he 
argued,  why  should  the  number  of  leucocytes  be  habitually  in- 
creased after  a  meal? 

His  reasoning  seemed  so  valid  that  he  has  a  good  many  fol- 
lowers. Cramer  and  Pringle,  for  example,  and  Noel  Paton  be- 
lieve that  the  leucocyte  plays  a  very  important  part  in  the  assim- 
ilation of  the  protein  food-products;  and  Pavy  elaborated  the 
hypothesis,  arguing  that  the  entire  conversion  of  the  food  pep- 
tones into  body  protein  is  brought  about  by  the  leucocytes. 

The  particular  type  of  leucocyte  believed  to  be  chiefly  involved 


MECHANISM   OF  PROTEIN   HYDROLYSIS  AND  IMMUNIZATION      35 

is  the  lymphocyte,  it  having  been  shown  by  Paton,  Goodal,  and 
Gulland  that  the  most  marked  postprandial  increase  in  leucocytes 
occurs  among  the  lymphocytes,  although  there  is  also  increase 
among  the  polymiclears.  My  own  researches,  as  will  appear 
presently,  show  that  the  large  monocyte  is  importantly  involved, 
particularly  when  the  parenteral  protein  to  be  dealt  with  includes 
the  full-sized  molecule,  as  frequently  happens. 

It  is  interesting  to  add  that  the  leucocytic  recruits  come,  ac- 
cording to  Paton  and  Goodal,  not  from  the  intestinal  lymphatic 
tissue,  but  from  the  marrow  of  the  bones.  Their  development 
is  stimulated,  we  must  assume,  either  (1)  directly  by  food  prod- 
ucts in  the  blood,  or  indirectly  (2)  through  the  agency  of  the 
sympathetic  nervous  system,  or  (3)  in  response  to  a  hormone 
sent  out  from  the  intestine.  It  is  conceivable  that  the  hormone 
that  produces  this  effect  is  the  secretin  of  the  duodenum,  which 
is  known  to  have  a  similar  stimulating  effect  on  the  secretions 
of  the  pancreas. 

Pavy  developed  the  hypothesis,  which  Noel  Paton  has  also 
advanced,  that  the  leucocytes,  after  synthesizing  the  proteins, 
undergo  autolysis,  thus  discharging  their  proteins  into  the  blood, 
to  furnish  material  for  the  tissue  cells. 

It  seems  probable  that  there  is  a  measure  of  truth  in  the  lat- 
ter part  of  this  hypothesis,  referring  to  the  autolysis  of  the  leu- 
cocyte. In  fact,  the  assumption  that  autolysis  occurs  seems 
unavoidable,  in  view  of  the  observed  rapid  fluctuations  in  the 
leucocytic  population  even  in  health.  But  it  is  highly  improb- 
able that  the  leucocyte  (in  its  mature  state)  synthesizes  pro- 
tein ;  or  that  the  main  function  of  handling  protein-products  of 
the  intestine  is  dependent  upon  the  leucocyte.  As  to  this,  Halli- 
burton's  suggestion,  to  the  effect  that  the  number  of  leucocytes 
in  the  blood  stream  is  inadequate  to  perform  this  function  in  its 
entirety,  seems  fairly  conclusive.  Halliburton  argues  that  the 
total  blood  stream  contains  only  about  one  gram  of  lymphocytes ; 
and  even  if  this  amount  were  doubled  during  digestion,  "it  is 
difficult  to  see  how  two  grams  of  lymphocytes  can  tackle  the 
enormous  burden  which  every  meal  must  put  upon  them."  It 
should  be  observed,  however,  that  the  quantity  of  foreign  protein 
in  the  blood  at  any  one  time  is  small.  But  the  aggregate  quantity 
of  serum  protein  is,  of  course,  relatively  enormous,  and  in  the 
last  analysis  it  is  clear  that  this  is  the  product  of  the  synthesis 
of  food  proteins. 

According  to  the  present  view,  the  leucocytes  are  not  called 
upon  to  "tackle"  this  problem,  which  is  handled  effectively  by 
the  mother  cells  that  generate  leucocytes  and  red  corpuscles, 
notably  the  latter.  These  mother  cells  (in  bone  marrow,  spleen, 
and  in  case  of  certain  leucocytes  lymphatics)  synthesize  protein 


36      THE    PROTEOMORPHIC    THEORY   AND   THE    NEW    MEDICINE 

from  its  ammo-acid  elements  in  great  quantity,  as  evidenced  in 
the  bodies  of  the  corpuscles  themselves.  But  the  province  of  the 
mature  corpuscles  is  to  deal  with  proteins  in  a  quite  different 
way. 

Their  task  is  not  that  of  synthesis  but  of  proteolysis,  and  it 
is  exercised,  not  only  (1)  in  connection  with  the  regular  supply 
of  food  proteids,  but  (2)  with  bacterial  proteins  and  (3)  with 
exceptional  increments  of  unbroken  or  only  partially  cleaved  pro- 
teins that  find  their  way  by  inadvertence  into  the  vascular 
mechanism. 

In  view  of  the  relatively  small  bulk  of  the  cells  making  up 
the  normal  leucocyte  population,  it  should  be  recalled  that  the 
amount  of  foreign  protein  in  the  blood  serum  at  one  time  has 
been  variously  estimated  between  a  minimum  of  .005  per  cent, 
and  a  maximum  of  0.12  to  0.19  per  cent. — say  from  three  to 
twelve  grams  in  a  person  of  average  size. 

In  my  original  statement  of  the  Proteomorphic  theory,  it  was 
suggested  that  the  polynuclear  leucocyte  deals  with  the  unbroken 
proteins  (bacterial  or  dietetic)  ;  the  red  corpuscle  with  partially 
cleaved  molecules  of  the  polypeptid  order ;  and  that  the  lympho- 
cyte inaugurates  the  decompounding  of  the  normal  serum  pro- 
teins, to  supply  energy  for  the  activities  of  the  digestive  organs, 
the  muscles,  and  the  tissues  in  general.  It  now  seems  to  me 
improbable,  however,  that  the  leucocytes  are  called  upon  to  deal 
with  the  normal  serum  proteins.  I  shall  revert  to  this  aspect  of 
the  matter  a  little  later. 

I  did  not  originally  attempt  a  more  detailed  analysis  of  the 
relative  share  of  the  different  types  of  white  corpuscles  in  the 
work  of  proteolysis.  My  subsequent  studies,  however,,  which  in- 
volved observation  of  the  modified  differential  count  in  several 
hundred  human  subjects  under  influence  of  foreign  proteins  in- 
troduced parenterally,  enabled  me  to  elaborate  the  thesis,  and 
to  develop  at  least  a  provisional  hypothesis  as  to  the  system  of 
division  of  labor  among  the  various  groups  of  the  leucocyte 
population. 

These  experimental  observations  and  conclusions  will  be  fully 
presented  in  later  chapters  of  the  present  work.  By  way  of 
anticipation,  I  may  say  here  that  they  give  the  strongest  possible 
support  to  the  general  thesis  of  the  Proteomorphic  theory  as  re- 
gards the  essential  proteolytic  activities  of  the  corpuscles.  They 
also  furnish  suggestive  clues  to  the  solution  of  sundry  problems 
as  to  the  differential  distribution  of  the  various  types  of  leuco- 
cytes, in  health  and  disease,  at  different  ages  in  the  human  sub- 
ject, and  among  different  orders  of  animals,  that  have  hitherto 
gone  quite  unsolved. 

In  point  of  fact,  very  little  is  definitely  known  as  to  the  pre- 


MECHANISM   OF  PROTEIN    HYDROLYSIS  AND  IMMUNIZATION      37 

cise  mutual  relations  of  the  different  types  of  leucocytes.  There 
is  a  general  impression  that  these  fall  into  two  groups,  one  of 
myelytic  origin  and  the  other  of  lymphatic  origin.  In  the  former 
group  are  the  basophiles,  the  eosinophiles,  the  large  mononuclears, 
and  the  neutrophiles.  In  the  latter  group  are  the  lymphocytes. 
Whether  or  not  the  lymphocytes  should  be  divided  into  small 
and  large,  as  two  different  classes,  is  a  matter  regarding  which 
the  authorities  are  not  agreed.  Also  the  question  of  the  precise 
origin  and  functions  of  the  large  monocytes  is  by  no  means 
settled.  Ehrlich  regarded  them  as  the  forms  which,  developing 
through  a  transitional  stage,  became  transmuted  to  polynuclears. 
But  it  does  not  appear  that  there  is  any  positive  evidence  in  sub- 
stantiation of  this  view. 

Furthermore,  it  has  been  disputed  as  to  whether  the  large 
lymphocytes  are  the  parent  forms  of  which  the  small  lympho- 
cytes are  the  daughter  cells;  or  whether,  on  the  other  hand,  the 
small  lymphocyte  grows  and  develops  into  a  large  lymphocyte. 

Meantime,  it  does  not  appear  that  any  one  has  given  close 
study  to  the  question  as  to  the  precise  material  out  of  which 
the  bodies  of  the  various  leucocytes  are  developed,  nor  as  to  the 
specific  distribution  of  their  protein  bodies  after  disintegration. 
It  has  been  observed  that  there  may  be  deviation  of  two  thousand 
or  three  thousand  leucocytes  to  the  cubic  millimeter  under  nor- 
mal conditions  in  the  course  of  a  day.  Reinart,  for  example,  gives 
the  average  number  of  leucocytes  at  six  o'clock  in  the  morning  as 
5,125;  and  the  average  at  4  P.M.  as  8,262.  If  we  may  accept 
such  a  variation  as  this  as  typical,  it  becomes  obvious  that  the 
growth  and  disintegration  of  three  thousand  leucocytes  to  the 
cubic  millimeter  as  a  normal  process  during  a  period  of  twenty- 
four  hours  involves  a  cycle  of  protein  metabolism  that  is  highly 
significant.  A  very  interesting  question — and  a  question  of  great 
importance — arises  as  to  whether  the  transmutation  of  raw  mate- 
rials, so  to  speak  (with  amino-acids  for  the  ultimate  building 
stones),  through  which  the  bodies  of  the  leucocytes  are  built  up 
takes  place  only  in  the  mother  organs  of  bone  marrow  and  lymph 
nodes,  or  whether  the  free  leucocytes  in  the  blood  stream  con- 
tinue to  grow  and  develop,  taking  to  themselves  food  pabulum, 
and  passing  through  stages  of  individual  development  that  may 
be  properly  spoken  of  as  juvinility,  maturity,  and  old  age. 

The  well-known  fact  that  the  larger  types  of  leucocytes  exer- 
cise a  phagocytic  function,  seeming  to  feed  on  the  bodies  of 
bacteria,  gives  strong  support  to  the  supposition  that  these  cells 
are  capable  of  ingesting  protein  pabulum  and  converting  it  into 
material  for  the  increment  of  their  own  particular  protein  sub- 
stance. It  is  believed  by  some  observers  that  the  granular  struc- 
ture of  the  leucocytes  commonly  spoken  of  as  myelocytic  (that 


38      THE    PROTEOMORPHIC   THEORY   AND   THE    NEW    MEDICINE 

is  to  say,  of  bone-marrow  origin)  represents  something  compar- 
able to  a  glandular  substance,  constituting  a  secreting  mechanism. 
The  secretions  in  question  are  supposed  to  be  enzymic  in  char- 
acter, representing  the  various  antibodies,  in  particular  the  so- 
called  complement. 

According  to  one  view,  the  granular  leucocytes  are  all  of  bone- 
marrow  origin,  and  constitute  a  class  apart.  But  this  view  is 
obviously  inconsistent  with  Ehrlich's  claim  that  the  large  non- 
granular  mononuclear  leucocytes  develop  individually  into  neu- 
trophiles. 

Evidence  in  the  matter  is  by  no  means  as  conclusive  as  could 
be  desired,  yet  it  is  universally  admitted  that  different  organs  of 
the  body  may  on  occasion  take  on  the  function  of  leucocyte- 
production;  and  it  may  very  well  be  questioned  whether  there 
is  any  such  distinct  and  fundamental  difference  between  the  blood- 
forming  cells  of  the  bone  marrow  and  the  similar  cells  of  the 
lymphatic  system  as  has  sometimes  been  suggested.  It  may  fairly 
be  assumed,  however,  on  embryological  grounds  that  the  lym- 
phatic system  constitutes  a  somewhat  more  primordial  structure 
than  the  bone  marrow,  inasmuch  as  the  latter  is  a  relatively  late 
development  in  the  fcetus.  But,  on  the  other  hand,  many  ob- 
servers are  disposed  to  trace  the  origin  of  the  primitive  forms  of 
cells  that  appear  in  the  blood  under  certain  abnormal  conditions 
(notably  the  leukaemias)  to  the  bone  marrow  rather  than  to  the 
lymphatic  system. 

It  is  more  than  likely  that,  when  the  systemic  disturbance  is 
sufficiently  profound,  both  sets  of  organs  may  revert  to  a  some- 
what primordial  manner  of  functioning,  and  put  out  cells  of  a 
more  embryonic  type  than  the  ones  usually  sent  into  circulation. 

By  way  of  anticipation,  I  may  say  that  in  a  later  chapter  of 
this  book  I  shall  suggest  an  hypothesis  of  the  specific  functions 
of  the  different  types  of  leucocytes  according  to  which  the  eosino- 
philes  deal  with  the  unbroken  protein  molecule,  the  large  mono- 
cytes  with  full  protein  molecules  and  proteoses,  the  small  lym- 
phocytes with  proteoses  and  peptones,  the  polynuclears  with 
peptones  and  polypeptids,  and  the  red  corpuscles  with  polypep- 
tids  and  amino-acids.  It  is  further  suggested  that  the  polynu- 
clears have  to  do  with  the  digestion  of  lipoids  and  fats. 

Details  as  these  elaborations  of  the  Proteomorphic  theory  can 
more  appropriately  be  given  after  the  general  preliminary  state- 
ment of  them,  to  which  the  present  chapter  is  chiefly  devoted, 
has  been  made.  Meantime,  however,  I  venture  again  to  depart 
from  chronological  sequence  to  the  extent  of  citing  two  series 
of  laboratory  investigation  by  independent  workers  that  have 
been  carried  out  since  the  original  publication  of  the  Proteomor- 
phic theory,  and  which  in  themselves  furnish  strong  presumptive 


MECHANISM    OF   PROTEIN    HYDROLYSIS  AND   IMMUNIZATION      39 

evidence  of  the  validity  of  (1)  the  general  thesis  that  the  cor- 
puscles deal  with  foreign  proteins,  and  (2)  the  important  feature 
of  the  theory  which  ascribes  to  the  red  corpuscles  the  work  of 
ultimate  proteolysis  and  oxidation  of  the  split  molecules  of  the 
order  of  polypeptids. 

The  experiments  that  (if  I  correctly  interpret  them)  throw 
corroborative  light  on  the  first-mentioned  aspect  of  the  Proteo- 
morphic  theory  were  made  by  Drs.  M.  W.  Man  waring  and  Yoshio 
Kusama,  of  the  Department  of  Bacteriology  and  Immunity  of 
Leland  Stanford,  Jr.,  University,  as  recorded  in  the  Proceedings 
of  the  Society  for  Experimental  Biology  and  Medicine,  of  May 
24,  1916.  These  experiments  go  to  show  that  the  blood  corpuscles 
of  a  rabbit  actively  absorb  goat  serum  proteins,  whether  the  goat 
serum  is  mixed  with  the  (defibrinated)  rabbit's  blood  in  a  recep- 
tacle outside  the  body  or  whether  it  is  injected  into  the  system  of 
the  living  rabbit. 

This  observation,  obviously,  gives  the  strongest  support  to  the 
assumption  of  the  Proteomorphic  theory  that  the  blood  corpuscles 
are  the  agents  chiefly  concerned  in  dealing  with  foreign  proteins ; 
the  assumption  that  forms  the  chief  basis  for  the  explanation  of 
the  therapeutic  action  of  the  proteal  remedies  with  which  the 
present  monograph  is  concerned. 

It  should  be  added  that,  in  the  experiments  just  cited,  it  is 
further  recorded  that  about  25  per  cent,  of  the  goat  protein  may 
remain  in  the  rabbit's  blood  serum.  "If  the  serum  and  cor- 
puscle fractions  (of  the  blood),  are  allowed  to  undergo  inde- 
pendent autolysis  (10  hrs.,  37°  C.)  a  distinct  restoration  of  the 
goat  protein  is  observed  in  each  fraction.  The  restoration  of 
the  protein  in  the  corpuscle  fraction,  however,  is  usually  much 
more  pronounced  than  that  in  the  serum  fraction,  and  may  amount 
to  as  much  as  50  per  cent,  of  the  total  protein  originally  added  to 
the  blood." 

From  this  it  would  appear  that  something  like  25  per  cent, 
of  the  goat  serum  originally  injected  is  unrecovered,  presumably 
having  been  hydrolyzed  to  a  stage  of  decomposition  at  which 
it  is  no  longer  recognized  as  goat  protein. 

It  would  appear  to  be  a  logical  inference  that  such  hydrolysis 
of  the  goat  serum  proteins  has  been  effected  by  enzymes  gen- 
erated in  the  bodies  of  the  corpuscles  which,  according  to  the 
observations  of  the  experimenters,  constituted  the  chief  medium 
for  absorption  of  the  foreign  proteins.  As  far  as  they  go,  these 
experiments  afford  direct  collaboration  of  one  of  the  principal 
theses  of  the  proteomorphic  theory. 

Possibly  it  may  seem  surprising  that  so  large  a  proportion  of 
the  goat  serum  proteins  remained  unhydrolyzed  after  10  hours' 
maceration.  It  must  be  obvious,  however,  that  corpuscles  under- 


40    THE  PROTEOM'ORPH  c  THEORY  AND  THE  NEW  MEDICINE 

going  autolysis  outside  the  body  may  have  far  less  enzymic 
activity  than  they  would  exhibit  under  normal  conditions.  But 
in  addition  to  this  it  should  be  observed  that  the  amount  of  goat 
serum  introduced  in  these  experiments  was  enormously  large  as 
contrasted  with  any  doses  of  foreign  protein  administered  thera- 
peutically  to  the  human  subject,  amounting,  in  fact,  to  one  per 
cent,  of  the  rabbit's  blood.  Assuming  that  the  goat  serum  com- 
prises at  least  20  per  cent,  of  proteins,  the  amount  of  foreign 
protein  thus  introduced  would  constitute  one-fifth  of  one  per 
cent,  of  the  total  bulk  of  the  rabbit's  blood. 

That  the  corpuscles  of  the  rabbit's  blood  were  able  to  absorb 
at  least  50  per  cent,  of  this  shows  remarkable  capacity  on  the 
part  of  the  corpuscles  for  handling  foreign  proteins  that  invade 
the  medium  in  which  they  lie. 

As  a  still  further  anticipation  of  matter  to  be  discussed  in 
detail  later,  it  may  be  noted  that  the  normal  proteals  under 
consideration  in  this  book  contain  only  3  mgm.  of  nitrogen  to 
the  cubic  centimeter,  or  the  equivalent  of  less  than  2  per  cent, 
of  vegetable  proteins.  Meantime  the  amount  of  this  2  per  cent, 
solution  of  proteins  used  in  a  hypodermic  dose  is  only  one  or 
two  cubic  centimeters,  as  a  rule ;  and  almost  never  more  than  3 
or  4  cubic  centimeters.  Such  a  dose,  introduced  into  the  large 
quantity  of  blood  in  the  human  body,  obviously  constitutes  an 
infinitesimal  protein  intrusion  in  comparison  with  the  one  per 
cent,  of  goat  serum  mixed  with  the  rabbit  blood  in  the  experi- 
ments of  Manwaring  and  Kusama. 

Since  these  experiments  now  give  us  an  inkling  of  the  capac- 
ity of  the  blood  corpuscle,  the  thought  not  unnaturally  suggests 
itself  that  possibly  we  have  hitherto  used  proteals  in  much  smaller 
doses  than  might  be  permissible  or  advantageous.  Here,  ob- 
viously, is  an  interesting  field  for  future  experimentation,  in 
connection  with  cases  that  have  proved  intractable  to  the  pro- 
teal  medication  as  hitherto  administered.  It  must  be  recalled, 
however,  that  it  has  been  customary  to  carry  the  dosage  to  the 
point  of  producing  an  anaphylactic  response,  and  that  with  most 
patients  this  is  likely  to  occur  with  a  dose  of  thirty  minims  or 
less  of  a  two  per  cent,  protein  solution.  On  the  other  hand,  in 
some  early  tests  that  antedated  the  beginning  of  proteal  therapy, 
an  experimenter  administered  doses  of  one  hundred  cubic  cen- 
timeters of  sheep-blood  serum  into  the  peritoneal  cavity  of  a 
cancer  patient,  with  seemingly  beneficial  results.  It  is  noteworthy 
that  the  severity  of  the  deferred  anaphylactic  reaction  (including 
chill)  is  by  no  means  determined  exclusively  by  the  quantity  of 
protein  administered.  It  has  already  been  noted  that  proteins 
to  which  the  system  has  not  been  habituated,  such  as  those  of 
alfalfa,  produce  relatively  strong  reactions. 


MECHANISM   OF   PROTEIN    HYDROLYSIS   AND   IMMUNIZATION      41 

The  second  laboratory  investigation,  to  which  reference  was 
just  made,  concerns  the  presence  of  uric  acid  in  the  red  cor- 
puscles. In  the  Journal  of  Biological  Chemistry,  August  20, 
1915,  Benedict  shows  that  uric  acid  exists  in  the  blood  in  two 
forms,  in  a  "free"  and  in  a  "combined."  Ox-blood,  which,  when 
tested  by  the  method  of  Folin,  hitherto  considered  reliable, 
showed  a  content  of  0.2  mgm.  of  uric  acid  per  100  c.mm.,  was 
found  as  a  rule  to  contain  in  reality  about  7  mgm.  of  total 
uric  acid  per  100  c.c.  of  blood,  practically  all  of  this  being  con- 
tained in  the  red  blood  cells.  "If  the  ox  blood  were  allowed  to 
stand  at  room  temperature  and  protected  from  bacterial  con- 
tamination, there  was  found  to  take  place  a  gradual  transition 
from  the  combination  to  the  free  form  of  uric  acid,  apparently 
due  to  the  action  of  some  ferment.  .  .  .  Benedict  suggests  that 
possibly  the  free  uric  acid  is  that  which  is  ready  for  excretion  as 
such,  while  the  combined  is  capable  of  further  catabolism." 
(Summary  appearing  in  Medical  Record.} 

It  must  be  obvious  that  this  finding  of  large  quantities  of  uric 
acid  in  the  red  cells  gives  strong  support  to  that  part  of  the  pro- 
teomorphic  theory  which  postulates  the  red  cells  as  the  seat  of 
the  enzymic  activities  which  accomplish  the  ultimate  decompound- 
ing of  the  protein  by-products.  Uric  acid  is  one  of  the  most  im- 
portant of  these  by-products.  It  chances  to  be  one  that  can  ulti- 
mately be  eliminated  by  way  of  the  kidneys ;  but  whether  the  red 
cells  excrete  it  into  the  blood  for  that  purpose,  or  whether  it 
merely  is  left  in  the  blood  stream  when  the  red  cell  is  disin- 
tegrated in  the  liver,  is  still  conjectural.  Meantime  Benedict's 
experiments  give  additional  evidence  that  the  red  cells  have  pre- 
cisely such  enzymic  functions  in  connection  with  the  later  stages 
of  decompounding  of  the  protein  molecule  as  the  proteomorphic 
theory  postulates. 

Possibly  a  few  words  of  further  exposition  and  interpretation 
may  be  desirable,  illustrating  a  little  more  in  detail  the  chemical 
aspects  of  the  observed  facts  in  connection  with  the  suggested 
explanation  along  the  lines  of  the  proteomorphic  theory. 

Note,  then,  that  the  chemical  formula  of  uric  acid  is  C5H4N4O3. 
Obviously  we  have  here  a  substance  not  distantly  related  to  some 
of  the  amino-acids,  but  proportionally  richer  in  nitrogen  than 
any  one  of  these,  the  only  one  approaching  it  in  this  regard 
being  arginine  (C6H14N4O2).  Another  significant  distinction  be- 
tween uric  acid  and  amino-acids  is  the  fact  that  it  contains  three 
atoms  of  oxygen  and  only  four  atoms  of  hydrogen.  There  is 
no  amino-acid  with  less  than  five  atoms  of  hydrogen;  and  all 
but  three  of  them  have  either  two  or  four  atoms  of  oxygen,  each 
of  the  three  exceptional  ones  having  only  a  single  atom  of 
nitrogen. 


42      THE   PROTEOMORPHIC   THEORY   AND  THE    NEW    MEDICINE 

We  have,  then,  in  uric  acid  a  compound  relatively  rich  in 
nitrogen  and  oxygen,  but  poor  in  hydrogen.  To  modify  it  by 
adding  a  molecule  of  water  would  probably  (in  view  of  the 
four  atoms  of  oxygen)  give  it  extreme  instability;  and  to  take 
a  molecule  of  water  away  from  it  would  deplete  its  hydrogen 
supply,  which  is  already  below  the  minimum  amino-acid  stand- 
ard. Uric  acid,  therefore,  appears  to  represent  an  end  product 
of  the  split  protein  molecule  of  such  structure  that  it  does  not 
afford  available  material  for  the  making  of  amino-acids — the  only 
form  of  nitrogenous  building  material  that  the  system  can  utilize 
in  its  synthetic  operation.  This  applies,  at  any  rate,  to  the  por- 
tion of  uric  acid  which  finally  appears  in  the  blood  plasma.  The 
red  blood  corpuscle  does,  apparently,  modify  a  part  of  the  orig- 
inal uric  acid  supply,  since  only  a  fraction  of  it  appears  in  the 
plasma. 

Similar  reasoning  applies,  seemingly,  to  those  other  waste- 
products  of  protein  metabolism,  urea  (CH4N2O)  and  bilurubin 
(C16H18N2O3)  ;  each  with  an  odd  number  of  oxygen  atoms;  one 
hopelessly  deficient  in  carbon  atoms,  the  other  with  an  excess  of 
them.  The  origin  of  bilurubin  as  a  product  of  the  destruction 
of  red  corpuscles  in  the  liver  has  long  been  known;  and  as  a 
matter  of  course,  it  received  consideration  in  the  development  of 
one  important  aspect  of  the  Proteomorphic  theory.  That  the 
observations  linking  uric  acid  with  the  red  corpuscles  were  made 
subsequently  to  the  putting  forth  of  the  Proteomorphic  theory, 
and  quite  independently,  gives  them  added  value  as  corrobora- 
tive of  the  truth  of  the  theory  itself. 

Meantime,  as  throwing  light  from  another  angle,  we  may  recall 
experiments  made  thirty  years  ago  by  Horbaczewski,  which 
showed  that  uric  acid  was  formed  during  the  digestion  of  spleen 
pulp  with  blood  in  the  presence  of  oxygen,  but  that  in  the  absence 
of  blood  only  the  purin  bodies  hypozanthin  and  zanthin  were 
formed ;  the  so-called  zanthin  oxydase  requisite  to  complete  the 
transformation  into  uric  acid  being  apparently  lacking.  It  seems 
a  plausible  inference  that  the  corpuscles  supply  this  oxydase,  since 
the  presence  of  blood  was  the  determining  factor  in  bringing 
about  the  final  oxidation  through  which  zanthin,  C5H4N4O2,  is 
transformed  into  uric  acid,  C5H4N4O3. 

This  observation,  linked  with  the  new  revelations  of  Benedict, 
above  cited,  makes  plausible  the  further  assumption  that  the  red 
corpuscles  (found  thus,  apparently,  to  have  an  essential  share 
in  the  genesis  of  uric  acid  from  purin  bases,  and  demonstrated 
as  the  chief  locus  of  uric  acid  after  it  is  formed),  are  the  source 
also  of  the  uricase  that  transforms  uric  acid  (by  removal  of  a 
molecule  of  the  carbonyl  group,  CO,  and  the  substitution  of  a 
molecule  of  H2O)  into  allantoin,  C4H0N4O3;  and  in  due  course 


MECHANISM    OF   PROTEIN    HYDROLYSIS   AND   IMMUNIZATION      43 

effects  the  hydrolysis  or  oxidation  of  each  molecule  of  allantoin 
(by  removal  of  two  molecules  of  CO2  and  substitution  of  a 
molecule  of  H2O)  into  two  molecules  of  urea,  CH4N2O,  the 
ultimate  waste  product  of  purin-bearing  proteins. 

If  this  assumption  is  valid,  a  still  clearer  view  is  gained  of  the 
modus  operandi  of  non-specific  proteins  as  therapeutic  agents  in 
dealing  with  rheumatoid  conditions  (commonly  believed  to  be 
associated  with  the  inadequate  catabolism  of  purin  bodies  and 
their  oxidation  product,  uric  acid),  and  with  malignant  neoplasms, 
the  structure  of  which  is  largely  made  up  of  purin-bearing  pro- 
teins. An  agent  which  stimulates  production  of  red  corpuscles 
and  enhances  their  enzymic  activities,  as  the  non-specific  pro- 
teins have  been  amply  demonstrated  to  do  in  my  hands  and 
those  of  my  associates,  should  theoretically  be  effective  in  pre- 
cisely those  conditions  in  which  the  proteals  have  been  observed 
to  have  clinical  value. 

Further  consideration  of  this  aspect  of  the  subject  must  be 
deferred,  however,  until  we  have  dealt  with  the  more  general 
fundamental  properties  concerned.  Taking  up  the  sequence  of 
the  original  presentation  of  the  Proteomorphic  theory,  we  may 
advantageously  make  inquiry  as  to  the  extent  to  which  foreign 
proteins  are  present  in  the  parenteral  system  under  usual 
conditions. 

PROTEOLYTIC  ACTIVITIES  OF  THE  LEUCOCYTE 

It  has  been  shown  by  various  experimenters  (Voit  and  Bauer, 
Haidenhain,  Friedlander,  Waymouth  Reid,  Ascoli  and  Vigano) 
that,  under  certain  conditions,  unmodified  food  proteins  may  find 
their  way  through  the  intestinal  walls  and  enter  the  general  cir- 
culation. It  is  against  these,  according  to  the  present  view,  that 
the  digestive  functions  of  the  various  types  of  leucocyte  are  exer- 
cised; the  work  of  the  leucocyte  with  these,  as  with  the  bacterial 
proteins,  being  a  work  of  proteolysis  strictly  comparable  to  that 
performed  by  the  digestive  ferments  in  case  of  proteids  in  the 
digestive  tract — with  certain  variations  to  be  noted. 

This  view  finds  strong  support  in  the  fact  that  one  at  least 
of  the  enzymes  found  in  the  body  of  the  leucocyte  is  closely  com- 
parable to,  if  not  identical  with,  the  trypsin  of  the  digestive 
canal.  It  is  possible,  according  to  some  experimenters,  that  syn- 
thetic activities  also  lie  within  the  capacities  of  these  enzymes 
(all  catalytic  phenomena  are  conceivably  reversible).  But,  as- 
suredly, their  habitual  province  is  to  break  down  or  cleave  this 
protein  molecule,  not  to  synthesize  it. 

It  is  known  that  the  unbroken  food  protein,  and  even  so  small 
a  cleavage  product  as  peptone,  do  not  exist  normally  in  the 


44      THE   PROTEOMORPHIC    THEORY   AND   THE    NEW    MEDICINE 

blood  stream.  The  peptones  of  the  digestive  canal  are  believed 
to  be  further  hydrolized,  with  the  production  of  amino-acids, 
in  their  passage  through  the  intestinal  wall.  The  leucocyte  accom- 
plishes the  same  cleavage  (or  at  all  events  the  early  parts  of  this 
cleavage)  in  the  case  of  foreign  proteins  that  come  to  it.  And 
the  quantity  of  these  is  sufficient  to  give  full  scope  for  the  leuco- 
cytic  activities;  for  experiments  show  that  the  intrusion  of  the 
unbroken  protein  molecule  must  be  an  extremely  common  inci- 
dent, even  if  it  cannot  be  considered  a  strictly  normal  one.  More- 
over, there  are  complications  involved  in  the  task  of  disposing 
of  these  unwelcome  visitors. 

The  first  of  these  complications  is  contingent  on  the  fact  that 
the  leucocyte  is  thus  called  upon  to  deal  with  large  protein  mole- 
cules of  many  types,  and  that  it  can  scarcely  be  supposed  to  be 
able  to  do  so  without  producing  toxic  cleavage  molecules  at  some 
stage  of  the  process  that  may  escape  from  its  substance — say 
through  dissolution  of  the  body  of  the  leucocyte  itself — and  con- 
taminate the  blood  plasma.  Even  though  the  original  protein 
was  in  the  form  of  a  wholesome  foodstuff,  say  protein  of  beef 
or  of  egg  or  of  milk,  there  is  always  possibility  that  in  its  de- 
compounding there  may  arise  combinations  of  molecules  that 
are  poisonous  to  the  tissues  of  the  organism. 

As  Vaughan  phrases  it,  there  is  a  poisonous  group  in  every 
protein  molecule. 

Possibly  it  would  be  correct  to  say  that  there  are  many  poison 
groups ;  but  Vaughan  finds  that  their  physiological  effects  are 
essentially  the  same  in  all  proteins.  He  has  attempted  to  isolate 
this  group  of  molecules  which,  in  its  free  state,  becomes  a  poison 
(so  he  believes)  on  account  of  the  avidity  with  which  it  disrupts 
other  protein  molecules.  In  the  purest  form  in  which  he  has 
been  able  to  isolate  this  group  (and  this  is  probably,  he  conceives, 
far  from  chemical  purity),  it  kills  guinea  pigs  of  from  two  hun- 
dred to  three  hundred  grams  weight,  when  injected  intracar- 
diacally  in  doses  of  half  a  milligram.  In  the  original  protein 
molecule,  it  is  held,  the  poisonous  group  is  physiologically  inert, 
because  it  is  combined  with  secondary  groups  called  side-chains. 
But  these  secondary  groups  are  detached  or  decompounded  in  the 
proteolysis  of  the  molecule ;  and  there  is  conceivable  danger  that 
during  this  process  the  poisonous  group  may  become  detached 
and,  diffusing  in  the  blood  stream,  exert  a  toxic  effect  on  the 
central  nervous  system.  There  are  no  observed  phenomena  asso- 
ciated with  the  therapeutic  parenteral  introduction  of  the  pro- 
teins that  suggest  this,  however,  unless  the  anaphylactic  reaction 
occasionally  induced  be  so  interpreted. 

The  danger  of  such  a  result  when  proteins  are  digested  in  the 
alimentary  tract  is  small,  because  the  poisonous  group  is  prob- 


MECHANISM    OF   PROTEIN    HYDROLYSIS   AND   IMMUNIZATION      45 

ably  not  readily  absorbed  through  the  intestinal  wall.  But  the 
leucocyte  itself  is  suspended  in  the  blood  stream,  and  it  must  on 
no  account  permit  the  formation  of  a  poisonous  group,  or  if  such 
is  formed  it  must  be  retained  within  the  substance  of  the  leuco- 
cyte until  it  is  further  transformed  and  rendered  innocuous,  or 
is  otherwise  guarded  (for  example  by  the  red  corpuscles)  or 
extruded  from  the  blood  stream. 

Something  as  to  what  this  implies  may  be  conceived  from  an 
attempt  to  visualize  the  protein  molecule,  even  in  the  vaguest 
way.  A  typical  protein,  for  example,  is  globin,  the  basis  of 
hemoglobin.  Plimmer  gives  this  formula  for  globin :  C72fl,  H1174, 
N194S3O214.  In  the  process  of  digestion,  this  enormously  large 
and  complex  molecule  undergoes  hydrolytic  cleavage  again  and 
again.  A  single  molecule  of  protein  thus  cleaved  (always  in  such 
a  way  that  each  new  molecule  contains  a  modicum  of  nitrogen 
along  with  the  other  elements)  makes  up  successively  molecules 
of  proteoses  and  of  peptones  and  polypeptids,  and  ultimately,  if 
the  cleavage  is  carried  far  enough,  the  disintegrated  fragments 
constitute  the  relatively  simple  amino-acids,  which  form  the 
building  stones  of  all  proteins,  and  of  which  almost  a  score  of 
different  types  are  now  known,  a  few  of  which  have  become  rea- 
sonably familiar  in  recent  medical  literature  under  the  names  of 
glycine,  alanine,  valine,  leucine,  tyrosine,  etc.  The  simplest  of 
these,  glycine,  has  the  formula  C2H5NO2 ;  but  the  others  are  not 
much  more  complex ;  leucine,  for  example,  being  fairly  typical, 
with  the  formula  C6H13NO2. 

It  will  be  seen  that  something  like  two  hundred  molecules  of 
the  amino-acids — each  with  its  single  atom  of  nitrogen — would 
result  from  the  final  cleavage  of  a  single  ordinary  protein  mole- 
cule. So  the  digestion  or  proteolysis  of  even  a  small  group  of 
protein  molecules  is  like  the  'tearing  to  pieces  of  a  building  com- 
posed of  many  thousands  of  individual  bricks,  stones,  and  timbers. 
It  is  obvious  that  the  task  thrust  upon  the  leucocytes  by  the  in- 
truding protein  molecule  is  by  no  means  a  simple  one.  Yet 
there  is  abundant  experimental  evidence  that  such  proteolysis 
of  an  invading  protein  does  take  place  parenterally ;  and  to  the 
present  writer,  at  any  rate,  it  seems  highly  probable  that  it  is 
the  blood  corpuscles,  rather  than  any  of  the  more  specialized 
tissues,  that  perform  this  function. 

The  fact  that  only  small  quantities  of  foreign  proteins,  if  ex- 
perimentally introduced  into  the  blood  stream,  are  transformed 
(the  major  part  being  excreted  by  the  kidneys  unchanged),  is 
obviously  consonant  with  the  relatively  small  bulk  of  the  leu- 
cocytes in  their  totality,  as  above  referred  to. 

To  be  sure,  there  do  remain  residual  molecules,  after  final 


46      THE   PROTEOMORPHIC  THEORY   AND  THE   NEW    MEDICINE 

cleavage  is  effected,  that  are  actually  toxic — though  not  in  the 
same  degree  as  the  artificially  produced  product  of  Vaughan. 
These  are  the  familiar  end  products  uric  acid,  urea,  and  creati- 
nine — substances  with  which  the  body  has  learned  to  cope  by 
bringing  about  their  early  elimination.  Save  for  this  small  residual 
portion,  the  protein  molecule  will  have  been  transformed  into 
amino-acid  foodstuffs  which,  we  may  suppose,  do  not  differ 
in  any  essential  particular  from  those  supplied  in  far  larger 
bulk  from  the  usual  digestive-tract  proteolysis  of  the  proteins, 
including  the  stages  of  dismemberment  effected  in  the  walls  of 
the  intestine  itself  during  absorption. 

So  much  has  been  said  about  the  toxic  molecule  elaborated 
in  the  course  of  protein  hydrolysis  in  Vaughan's  laboratory  ex- 
periments that  it  is  desirable  to  call  attention  to  the  fact  that 
this  is  an  artificial  product  devised  by  special  manipulation.  The 
possibility  that  similar  toxic  molecules  are  developed  in  normal 
proteolysis  of  the  protein  molecule  has  been  considered  above. 
But  experience  shows  that  if  such  toxic  molecules  are  indeed 
developed,  short  of  the  familiar  end  products  (of  which  there 
is  no  evidence),  they  are  handled  in  such  a  way  as  to  shield 
the  system  against  untoward  consequences.  The  entire  thera- 
peutic procedure  under  discussion  in  the  latter  part  of  this  vol- 
ume (namely,  Proteal  therapy)  is  based  on  the  hypodermic  in- 
jections of  foreign  proteins.  Toxic  results  (aside  from  a  tem- 
porary anaphylactic  reaction)  have  not  been  observed. 

Moreover,  in  experimentally  testing  the  Proteals  I  have  admin- 
istered vegetable  proteins  of  many  types  hypodermically  to  small 
(400  to  800  gram)  guinea  pigs  day  after  day  in  doses  of  20  to 
30  milligrams,  with  no  harmful  effects  whatever.  The  animals 
thrive  under  the  treatment,  proving  conclusively  that  there  are 
no  toxic  molecules  developed  in  the  natural  hydrolysis  of  these 
vegetable  proteins  with  which  their  corpuscles  (or  other  tissues) 
cannot  adequately  cope. 

It  should  be  recalled,  however,  that  the  proteins  with  which 
these  therapeutic  tests  and  animal  experiments  are  made  all 
have  their  origin  in  vegetables  not  far  removed,  botanically,  from 
food  plants,  and  hence  are  relatively  non-toxic.  This,  however, 
does  not  greatly  change  the  argument,  since  (as  above  stated) 
Vaughan  liberates  his  toxic  molecule  from  various  types  of  pro- 
tein indifferently.  From  the  standpoint  of  practical  therapeutics, 
so  far  as  present  evidence  carries  us,  this  toxic  molecule  is  a 
negligible  quantity  in  non-specific  protein  therapy.  The  admin- 
istration of  the  Proteals  day  after  day,  for  a  term  of  months, 
to  patients  who  improve  steadily  in  blood  conditions  and  in  gen- 
eral health,  sufficiently  establishes  that  important  point. 


MECHANISM  OF  PROTEIN  HYDROLYSIS  AND  IMMUNIZATION    47 

THE  LEUCOCYTE  AND  BACTERIAL  PROTEINS 

But  the  task  of  the  corpuscles  in  shielding  the  tissues  against 
the  intrusion  of  unwelcome  proteins  in  non-assimilable  form 
becomes  enormously  complicated  when  the  proteins  in  question 
are  of  unfamiliar  types  and  are  encased  in  protective  cell  walls 
— in  other  words,  when  they  make  up  or  enter  into  the  bodies 
of  bacterial  invaders.  As  already  pointed  out,  however,  the 
capacity  of  the  leucocyte  to  engulf  these  bodies  and  to  digest 
them  and  make  them  part  of  its  own  substance  is  not  at  all  a 
matter  of  theory,  but  a  matter  of  observation  under  the  micro- 
scope. 

According  to  the  present  view,  there  is  no  fundamental  differ- 
ence between  the  digestion  of  the  bacterial  proteins  and  of  any 
other  type  of  protein — say  a  morsel  of  muscle.  There  are  prac- 
tical difficulties  to  be  solved,  such  as  getting  through  the  cell 
wall  of  the  bacterium,  but  the  transformation  of  its  protein, 
through  cleavage,  into  amino-acids  is  a  process  of  the  same  gen- 
eral type  as  any  other  proteolysis. 

As  qualifying  this  statement  somewhat,  however,  it  should  be 
borne  in  mind  that  no  two  proteins  from  different  sources — from 
the  bodies  of  different  species  of  animals  for  example — are  iden- 
tical as  to  all  their  groupings  of  molecules.  Dr.  Nuttall's  remark- 
able precipitin  experiments  show  how  marvelously  the  specificity 
of  proteins  holds  throughout  the  animal  kingdom.  The  highly 
interesting  demonstration  in  the  transplantation  of  organs  from 
one  animal  to  another  made  by  Dr.  Alexis  Carrel  evidence  the 
same  thing  from  a  quite  different  angle.  This  aspect  of  the  sub- 
ject is  so  important,  and  its  bearing  in  the  ultimate  problems  of 
protein  therapy  is  so  significant,  that  it  will  be  well  to  present  here 
a  brief  review  of  the  two  groups  of  experiments  in  question, 

TRANSPLANTING  ORGANS 

Dr.  Carrel  has  shown  that  the  lost  members  of  a  higher  animal 
may  be  replaced  by  the  substitution  of  a  new  member  through 
a  surgical  procedure.  He  has  amputated  the  leg  of  a  dog,  for 
example,  and  replaced  the  member  with  a  closely  similar  one 
taken  from  another  dog;  and  has  seen  the  new  member  grow 
into  place  and  become  a  part  of  the  body  of  its  new  host. 

Dr.  Carrel  has  similarly  transplanted  various  internal  organs, 
including  the  kidneys,  from  one  animal  to  another,  and  caused 
them  to  take  root,  as  it  were,  and  perform  their  normal  func- 
tions. The  success  of  his  experiments  is  due  largely  to  his 
introduction  of  a  new  method  of  uniting  arteries  and  veins, 
whereby  they  are  so  cleverly  sutured  together  that  scarcely  a 
trace  of  the  point  of  union  remains  when  the  wound  has  healed. 


48      THE   PROTEOMORPHIC  THEORY   AND  THE    NEW    MEDICINE 

From  the  present  standpoint,  the  thing  of  chief  interest  is 
that  Dr.  Carrel's  observations  show  that  there  is  a  specific  quality 
about  the  tissues  of  an  animal  that  is  profound  and  individual. 
The  kidney  of  a  cat  seems  to  perform  identically  the  same  func- 
tion as  the  kidney  of  a  dog.  But  one  cannot  be  substituted  for 
the  other  in  these  experiments  in  transplanting  members.  The 
kidney  of  a  dog  may  be  transferred  to  another  dog;  the  kidney 
of  a  cat  to  another  cat ;  but  the  two  must  not  be  interchanged. 

Even  where  the  organ  experimented  with  is  so  simple  as  the 
tube  of  an  artery,  it  is  with  difficulty  that  an  exchange  between 
animals  of  different  species  may  be  effected.  To  all  casual  obser- 
vation, and  even  to  close  observation  with  the  microscope,  the 
artery  of  a  cat  seems  identical  with  that  of  a  dog;  but  there  is 
a  deep-seated  chemical  difference  which  makes  itself  felt  if,  for 
example,  a  section  of  cat's  artery  is  made  to  replace  an  exsected 
portion  of  the  artery  of  a  dog. 

It  was  a  foregone  conclusion,  therefore,  that  the  attempt  re- 
cently made  by  a  Berlin  surgeon  to  replace  a  diseased  human 
kidney  with  the  kidney  of  a  monkey  would  be  a  failure.  The 
surgeon  of  the  future  will  doubtless  replace  diseased  kidneys 
and  other  vital  organs  with  normal  ones,  but  the  substituted 
organs  will  be  taken  from  human  subjects — say  from  the  vic- 
tims of  accidents,  or  from  executed  criminals. 

TRACING  BLOOD  RELATIONSHIP 

The  specific  quality  which  thus  pervades  every  tissue  of  an 
organism — so  that  the  remotest  cell  of  a  cat,  for  example,  has 
some  quality  of  felineness  that  distinguishes  it  from  a  cell  of 
any  other  species  of  animal — extends  its  mysterious  influence  so 
comprehensively  that  it  includes  not  merely  every  fiber  of  the 
organism,  but  every  drop  of  blood  in  an  animal's  body. 

The  proof  of  this  has  been  given  by  Professor  G.  H.  F.  Nut- 
tall,  the  American  biologist,  now  of  the  University  of  Cam- 
bridge, in  the  series  of  experiments  just  referred  to. 

Professor  Nuttall  has  developed  a  system  of  blood  testing  of 
such  delicacy  as  quite  to  transcend  the  bounds  of  microscopic 
examination  or  of  any  chemical  methods  hitherto  known;  and  in 
so  doing  has  found  a  method  of  testing  the  relationships  of  dif- 
ferent tribes  of  animals  that  seems  little  less  than  magical. 

The  tests  show,  for  example,  that  man  is  more  closely  related 
to  the  old-world  monkeys  than  to  the  monkeys  of  the  new  world ; 
our  closest  relatives  being  the  chimpanzee,  the  gorilla,  and  the 
orang  in  the  order  named.  Similarly  the  relationships  between 
different  members  of  the  dog  family,  the  cat  family,  and  the 
like,  are  traced.  Thus  the  hyena  appears  to  be  to  some  extent 


MECHANISM    OF   PROTEIN    HYDROLYSIS   AND    IMMUNIZATION      49 

intermediate  between  dog  and  cat  tribes,  but,  contrary  to  what 
might  be  expected,  it  is  much  more  closely  related  to  the  cat 
than  to  the  dog.  The  seal  and  sea  lion,  on  the  other  hand,  are 
closer  to  the  dog  family  than  to  the  cats.  Moreover,  the  seals 
are  somewhat  more  closely  related  to  the  weazel  tribe  than  to 
the  felines. 

The  porpoise,  which  might  be  supposed  to  be  allied  to  the 
seal,  is  found  instead  to  show  close  affinities  with  the  ox  tribe, 
and  in  particular  with  the  pigs.  Indeed  the  porpoise  may  be 
regarded  as  a  pig  that  has  taken  to  the  water  and  perforce  be- 
come carnivorous  in  diet.  It  is  necessary  also  to  record  the 
rather  unflattering  observation  that  the  blood  of  the  porpoise 
shows  more  pronounced  affinities  with  human  blood  than  with 
that  of  most  other  animals. 

The  family  groupings  among  reptiles  show  close  blood  rela- 
tionship between  lizards  and  serpents,  and  a  slightly  less  close 
relationship  between  turtles  and  crocodiles.  The  reptiles  are 
more  closely  related  to  birds  than  to  mammals.  The  relation- 
ship appears  to  be  particularly  close  between  birds  and  turtles; 
less  close  between  birds  and  crocodiles ;  the  avian  relationship 
with  lizards  and  serpents  being  still  more  remote. 

These  tests  singularly  confirm  the  conclusions  of  the  zoologist, 
based  on  study  of  the  anatomical  structures  of  the  different  tribes 
of  animals ;  but  the  testimony  is  absolutely  independent,  the  tests 
being  made,  as  already  pointed  out,  by  means  of  blood  alone. 

Indeed  the  maker  of  the  test  may  never  have  seen  a  specimen 
of  the  species  whose  rank  in  the  organic  scale  he  is  determining. 
The  specimens  of  blood  that  Professor  Nuttall  used  in  his  classi- 
cal series  of  experiments  were  collected  from  a  multitude  of 
sources;  no  fewer  than  seventy  different  persons  sending  speci- 
mens from  different  parts  of  the  globe. 

Many  of  the  collectors  were  hunters,  who  merely  dipped  a 
piece  of  filter  paper  in  the  blood  of  a  quarry  and  transmitted 
it  to  the  Cambridge  Laboratory.  There  the  discolored  piece  of 
paper  was  soaked  in  water  to  produce  a  clear  solution  of  blood 
serum.  A  portion  of  this  solution  was  placed  in  a  test-tube,  and 
this  test-tube  put  in  a  rack  along  with  scores  of  other  specimens, 
each  bearing  only  a  number. 

Into  each  test-tube  a  small  drop  of  a  certain  liquid  was  placed. 
If  the  solution  in  the  test-tube  became  cloudy,  the  experimenter 
was  able  to  pronounce  definitely  that  the  blood  was  that  of  an 
animal  of  a  certain  tribe.  It  might,  for  example,  be  the  blood 
of  a  tiger  or  a  leopard  or  a  panther  or  a  cheetah;  but  it  could 
not  be  the  blood  of  a  hyena  or  a  wolf  or  a  dog. 

Again  the  test  might  be  applied  to  a  blood  stain  on  a  hand- 
kerchief or  knife,  or  on  a  fragment  of  wood  from  a  floor  or 


50      THE   PROTEOMORPHIC  THEORY   AND  THE    NEW    MEDICINE 

window  sill,  or  scraped  from  the  surface  of  a  boot  or  a  coin.  In 
this  case  the  question  as  to  whether  the  stain  was  caused  by 
human  blood  or  by  that  of  some  animal  might  be  the  deciding 
testimony  in  a  murder  trial. 

Here  the  method  of  procedure  would  be  the  same  as  before. 
A  solution  being  made  from  the  blood  stain  and  placed  in  a 
test-tube,  the  trial  fluid  would  determine  whether  the  stain  was 
due  to  human  blood.  If  the  test  proved  negative,  other  tests 
might  determine  what  particular  animal  supplied  the  blood.  In 
a  case  reported  by  Professor  Uhlenroth,  for  example,  a  blood 
spot  in  the  road,  suspected  to  be  of  human  origin,  was  found  to 
be  from  the  blood  of  a  pig.  In  another  case  blood  stains  on  a 
garment  were  reported  as  being  partly  human  and  partly  due 
to  the  blood  of  the  sheep.  In  this  case  it  was  subsequently  proved 
in  court  that  the  wearer  of  the  garment  had  committed  a  mur- 
der, but  that  he  had  slaughtered  sheep  two  weeks  before  the 
murder. 

How  THE  TEST  FLUIDS  ARE  DEVELOPED 

A  word  now  as  to  the  production  of  the  magical  fluid  with 
which  such  tests  are  operated.  The  fluid  consists  of  a  portion 
of  blood  serum  drawn  from  the  veins  of  a  rabbit.  The  peculiar 
properties  of  the  serum  have  been  developed  by  repeated  injec- 
tions into  the  system  of  the  serum  of  human  blood  or  that  of 
some  other  member  of  the  animal  kingdom,  according  to  the 
particular  type  of  test  that  is  to  be  made. 

A  rabbit  inoculated  with  human  blood  develops  a  so-called 
anti-human  serum.  Another  rabbit  inoculated  with  the  blood 
serum  of  a  cat,  will  develop  an  anti- feline  serum;  and  so  for 
all  other  tribes  of  animals — including  not  merely  mammals,  but 
birds,  reptiles,  and  even  crustaceans,  such  as  the  lobster  and  its 
allies. 

The  explanation  of  the  development  in  the  body  of  the  rabbit 
of  the  peculiar  quality  of  blood  that  gives  the  anti-serum  its 
value  in  such  tests  as  those  outlined,  is  found  in  the  fact  that 
the  blood  of  almost  any  animal  has  a  certain  quality  of  toxicity 
when  injected  into  the  veins  of  an  animal  of  different  species. 
In  some  cases  this  action  may  be  very  virulent. 

For  example,  fifteen  drops  of  the  blood  of  an  eel  injected  into 
the  veins  of  a  dog  weighing  about  thirty  pounds  may  produce 
death  in  seven  or  eight  minutes. 

In  another  experiment  ten  drops  of  the  blood  serum  of  an  eel 
killed  a  rabbit  of  ordinary  size  in  two-and-a-half  minutes.  The 
foreign  blood  serum  appears  to  attack  the  blood  corpuscles,  ren- 
dering them  functionless  and  presently  dissolving  them. 


MECHANISM    OF   PROTEIN    HYDROLYSIS   AND    IMMUNIZATION       51 

Curiously  enough  the  blood  corpuscles  of  new-born  rabbits 
are  much  more  resistant  to  foreign  blood  than  are  those  of  the 
adult  rabbit.  But  a  certain  degree  of  resistance  obtains  in  all 
animals,  and  this  may  be  accentuated  by  introducing  a  very  small 
quantity  of  foreign  blood  serum,  and  from  time  to  time  repeat- 
ing and  increasing  the  dose.  In  this  way  the  system  of  the 
animal  becomes  to  some  extent  immune  to  the  poisonous  effect 
of  the  foreign  blood,  through  development  of  what  for  want  of 
a  better  term  is  called  an  anti-serum. 

The  blood  of  a  rabbit  that  has  attained  this  condition  may 
then  be  used  in  testing  for  the  presence  of  the  particular  type 
of  blood  that  was  used  in  developing  the  anti-serum.  For  ex- 
ample, if  human  blood  was  the  kind  injected  into  the  system 
of  the  rabbit,  the  rabbit's  blood  will  now  serve  as  a  test  for 
human  blood. 

MAN'S  REMOTE  RELATIVES 

It  appears,  however,  that  the  anti-serum  thus  developed,  while 
its  most  pronounced  reactions  will  be  given  with  solutions  of 
human  blood,  will  also  react  in  a  less  marked  degree  with  the 
blood  of  other  animals. 

If  successive  drops  of  the  anti-serum  are  introduced  into  one 
test-tube  after  another,  as  in  Dr.  Nuttall's  experiments,  it  will 
be  observed  that  in  some  tubes  there  is  an  immediate  reaction, 
resulting  in  a  white  precipitate.  In  other  tubes  the  reaction 
will  set  in  only  after  some  minutes;  in  yet  others  after  hours; 
and  the  remaining  test-tubes  will  remain  permanently  clear.  It 
is  these  graded  results  that  enable  the  experimenter  to  test  the 
blood  relationships  of  the  different  animals. 

It  is  found,  for  example,  that  when  a  test  is  made  with  human 
anti-serum,  an  immediate  reaction  is  observed  only  in  test-tubes 
containing  human  blood.  Less  prompt  and  less  marked  reaction 
occurs  in  the  tubes  containing  the  blood  of  the  man-apes;  still 
milder  reaction  in  the  case  of  baboons,  monkeys,  and  marmosets 
in  succession ;  and  a  long  delayed  or  altogether  negative  result 
in  all  other  cases.  It  is  obvious  how  similar  tests  with  other 
types  of  anti-sera  enable  the  experimenter  to  follow  out  the 
relationships  of  different  tribes  of  animals. 

Professor  Nuttall's  experiments  comprised  sixteen  thousand 
individual  tests,  with  a  total  of  at  least  586  species — mammals, 
birds,  reptiles,  batrachian,  fishes,  crustaceans — coming  from  all 
parts  of  the  globe.  These  experiments  are  in  themselves  highly 
interesting;  in  their  implications  they  are  nothing  less  than  as- 
tounding. 

Doubtless  some  hundreds  of  thousands  of  years  have  elapsed 


52      THE   PROTEOMORPHIC  THEORY   A*TD  THE   NEW    MEDICINE 

since  the  direct  ancestors  of  men  branched  from  a  common  stem 
with  the  direct  ancestors  of  the  gorilla.  There  has  been  no  blend- 
ing of  blood  in  the  intervening  centuries.  Cats  have  been  cats 
and  dogs  dogs  from  geological  epochs  so  remote  that  we  hesi- 
tate to  guess  their  span  in  terms  of  years.  So  the  intimate  chem- 
ical qualities  that  denote  man  or  ape  or  cat  or  dog,  each  in  con- 
tradistinction to  all  the  others,  must  have  been  transmitted 
unmodified  through  countless  thousands  of  generations. 

It  taxes  credulity  to  believe  that  such  intangible  properties 
could  be  transmitted  unmodified  through  the  blood  streams  of 
such  myriads  of  individuals ;  but  the  evidence  of  the  test-tubes 
proves  that  this  has  been  done. 

What  makes  the  marvel  greater  is  the  fact  that  the  bodies 
of  the  animals  have  meantime  been  so  modified  as  to  develop 
utterly  divergent  species — for  example,  the  lion,  the  tiger,  the 
puma,  the  leopard,  and  the  house  cat;  different  types  of  dogs, 
wolves,  foxes,  and  their  allies.  But  in  each  case  some  intangible 
quality  of  the  blood  remains  unchanged  to  prove  the  common 
origin.  Blood  is  indeed  thicker  than  water. 

THE  SOURCE  OF  SPECIFIC  ANTIBODIES 

In  making  the  above  presentation  of  the  experiments  showing 
the  specificity  of  proteins,  I  have  drawn  on  the  text  of  one  of 
my  popular  books,  Miracles  of  Science,  which  appeared  not 
long  before  the  original  publication  of  the  Proteomorphic  theory. 
I  have  thought  it  well  to  present  this  detailed  account  of  the 
precipitin  experiments,  because  they  bear  so  fundamentally  on 
the  essential  problem  of  the  protein  response  in  therapeutics,  the 
elucidation  of  which  is  the  chief  purpose  of  the  present  book. 

These  experiments  make  it  clear  that  the  phrase  "non-specific 
proteins,"  notwithstanding  its  convenience,  is  in  the  final  anal- 
ysis a  misnomer.  Proteins  may  be  used  non-specifically,  but  no 
two  are  precisely  alike.  Making  present  application  of  this  prin- 
ciple, and  recalling  that  the  single  enzyme  trypsin  is  observed 
to  begin  the  digestion  of  many  types  of  protein,  it  must  be  sup- 
posed that  the  exact  steps  of  the  successive  metamorphoses  are 
somewhat  different  in  each  case.  It  is  even  possible  that  there 
are  various  types  of  the  enzymes  that  now  go  by  the  name 
trypsin,  each  one  adapted  to  deal  with  a  different  protein.  But 
this  is  only  conjectural,  as  the  chemistry  of  the  enzymes  is  still 
very  obscure. 

Be  that  as  it  may,  however,  it  is  certain  that  each  type  of 
protein  undergoing  parenteral  digestion  and  assimilation  evokes 
from  the  digestive  mechanism  a  unique  response,  which  finds 
expression  in  the  secretion  into  the  blood  stream  of  specific  types 


MECHANISM   OF  PROTEIN    HYDROLYSIS  AND   IMMUNIZATION      53 

of  antibodies.  These  specific  antibodies  are  no  mere  by-products 
of  the  cleavage  of  the  foreign  proteins,  as  was  once  supposed. 
They  are  chemical  compounds  put  forth  by  the  defensive  mechan- 
ism and  having  such  specific  properties  as  will  enable  them  to 
antagonize  the  particular  protein  that  evoked  them.  This  is 
equally  true  of  proteins  of  every  type — of  the  molecules  that 
make  up  the  most  wholesome  foodstuff,  no  less  than  of  those 
that  make  up  the  most  virulent  bacillus. 

The  chemicals  in  question  are  known  as  bactericides,  bacterio- 
lysins,  hemolysins,  agglutinins,  precipitins,  and  opsonins.  Some 
of  these  names  may  be  duplications,  but  the  existence  of  a  cer- 
tain number  of  what  may  conveniently  be  termed  "antibodies," 
developed  through  response  of  the  organism  to  the  intrusion  of 
the  foreign  proteins,  is  a  chemical  fact  supported  by  unassailable 
evidence,  quite  apart  from  any  theory  whatever  as  to  the  pre- 
cise bodily  mechanism  through  which  they  are  produced.  We 
have  just  seen  this  illustrated  in  detail  in  the  case  of  Dr.  Nut- 
tail's  precipitins. 

But  when  we  attempt  to  localize  this  mechanism,  we  find  our- 
selves at  once  involved  in  difficulties.  To  be  sure,  the  line  of 
reasoning  just  presented  seems  to  point  rather  clearly  to  the  leu- 
cocyte as  the  developer  of  the  antibodies;  inasmuch  as  that  cell 
is  known  to  be  the  digester  of  the  offending  protein  itself.  But 
if  we  seek  direct  proof,  we  find  the  evidence  not  altogether 
convincing.  Nevertheless  a  number  of  observations  have  been 
recorded,  as  to  the  result  of  direct  experiments,  that  are  at  least 
highly  suggestive. 

Thus,  for  example,  Ruffier  and  Crendiropoulo,  as  cited  by  Nut- 
tall,  found  evidence  that  agglutinins  may  exist  in  the  leucocytes 
of  rabbits  and  guinea  pigs,  inasmuch  as  an  extract  of  leucocytes 
from  an  immune  animal  had  greater  agglutinating  power  than 
did  the  same  animal's  serum.  The  observations  of  Metchnikoff 
convinced  him  that  the  output  of  "fixatives"  varies  directly  with 
the  degree  of  phagocytosis.  Gengou,  following  up  Metchnikoff's 
conception  at  the  Pasteur  Institute,  "concluded  that  the  hemo- 
lysins are  derived  from  leucocytes,  for  the  reason  that  plasma 
separated  from  fresh  blood,  when  cooled  throughout,  by  cen- 
trifugalization,  was  less  hemolytic  than  serum."  The  experiments 
on  which  this  last  conclusion  were  based  were  repeated,  however, 
by  Ascoli,  with  opposite  results,  and  Pfeiffer  and  Marx  found 
antibodies  less  abundant  in  the  ground  bodies  of  leucocytes  of 
immunized  animals  than  in  the  plasma. 

Again,  according  to  a  recent  analysis  of  Gay  and  Rusk,  "the 
work  of  Deutsch,  Castellani,  Rath,  Weil  and  Braun,  and  Kraus 
and  Schiffmann  all  shows  that  the  agglutinins  appear  in  the 
blood  serum  before  they  are  present  in  the  extract  of  any  organ." 


54      THE    PROTEOMORPHIC    THEORY    AND   THE    NEW    MEDICINE 

But  "although  Gruber  originally  suggested  that  the  polymor- 
phonuclears  form  the  agglutinins  no  experimental  evidence  goes 
to  prove  this,  and  the  experiments  of  Achard  and  Bensaud,  Widal 
and  Sicard,  of  Paetsch,  and  of  Kraus  and  Schiffmann  all  seem 
to  disprove  leucocytic  or  local  origin." 

"Sweet  found  that  he  could  increase  the  complement-content 
by  the  injection  of  substances  having  a  positive  characteristic 
action  on  leucocytes."  (Nuttall.) 

As  to  precipitins  there  are  experiments  by  several  observers 
(including  Cantacuzene  and  Swerew,  Hiss  and  Zinsser,  and  Sten- 
strom)  seeming  to  point  to  the  leucocytes  as  a  definite  source ; 
and  Kraus  and  Schiffmann  "emphatically  regard  the  blood  as  the 
source  of  precipitins."  Here  again  there  is  contradictory  evi- 
dence; but,  on  the  whole,  it  may  be  said  that  a  strong  case  is 
made  out  for  the  leucocyte  as  the  source  of  precipitins  and  agglu- 
tinins, and  a  somewhat  less  convincing  case  for  bacteriolysins 
and  hemolysins.  I  shall  have  occasion  presently  to  refer  more 
at  length  to  some  recent  experiments  of  J.  W.  Vaughan,  in  which 
antibodies  evoked  by  cancerous  tissues  were  definitely  located  in 
the  large  mononuclear  leucocytes. 

Meantime  it  is  to  be  noted  that  a  considerable  number  of  the 
workers  who  failed  to  localize  the  immune  bodies  in  the  leuco- 
cytes found  evidence  for  their  localization  in  one  or  another  of 
the  leucocyte- forming  tissues — the  spleen,  the  lymphatics,  and  the 
bone  marrow.  Thus,  according  to  Nuttall,  "Shibayamia  found 
hemolysin  for  dog  corpuscles  in  the  spleen  and  lymphatic  glands 
of  normal  guinea  pigs,  not  elsewhere." 

Again  Gay  and  Rusk  interpret  the  work  of  Pfeiffer  and  Marx 
as  seeming  "to  indicate  very  clearly  that  the  protective  antibodies 
directed  against  the  cholera  spirillum  are  elaborated  in  the  leuco- 
poietic  organs,  particularly  in  the  spleen,  but  to  a  less  extent 
in  the  bone  marrow,  inasmuch  as  extracts  of  these  organs  pro- 
tect guinea  pigs  from  infection  before  the  blood  serum  does. 
Deutsch  essentially  corroborated  these  findings  with  B.  typhosus 
and  Castellani  with  B.  dysenteriac.  .  .  .  These  authors  agree 
that  the  spleen  is  not  essential,  as  its  removal  at  best  but  slightly 
inhibits  antibody  formation;  the  bone  marrow  and  lymph  nodes 
are  secondarily  concerned." 

As  to  hemolysins,  we  find  this  comment:  "Among  the  fixed 
tissues,  the  liver  and  spleen  seem  to  have  shared  the  honors  as 
the  possible  sites  of  hemolysin  formation.  Leuckhardt  and  Becht, 
following  the  work  of  Hektoen  and  Carlson,  found  that  the 
spleen  alone  of  the  organs  of  a  dog  that  has  received  goat  or 
rat  corpuscles  24  hours  previously  has  the  property  of  immuniz- 
ing new  animals."  But  this  experiment  is  not  considered  con- 


MECHANISM   OF   PROTEIN    HYDROLYSIS  AND   IMMUNIZATION      55 

elusive.  "Carrel  and  Ingebrister  have  produced  hemolysins  in 
the  growing  embryonic  spleen."  As  to  agglutinins,  it  is  noted 
that  "there  is  some  evidence  of  agglutinin  formation  in  the  spleen 
offered  by  V.  Emden,  Jatta,  and  Girgoleff."  • 

All  this  is  interesting;  but  there  are  contradictory  experiments 
all  along  the  line,  and  Gay  and  Rusk  do  not  regard  the  evi- 
dence on  the  whole  as  conclusive.  They  say,  however,  "there 
seems  greatest  agreement  on  the  point  that  antibodies  are  formed 
either  by  the  leucocytes  or  the  leucocyte- forming  organs.  And 
yet  a  good  deal  of  recent  work  points  with  increasing  emphasis 
to  the  liver,  an  organ  which,  in  view  of  its  other  functions,  might 
logically  likewise  serve  to  produce  antibodies. 

It  will  appear  that  the  conflicting  testimony  is  largely  har- 
monized so  soon  as  we  take  account  of  the  red  corpuscles  along 
with  the  leucocytes  and  cytogenic  system.  For  the  moment,  how- 
ever, it  suffices  to  point  out  that  all  the  different  experimenters 
are  at  one  in  designating  either  (1)  the  leucocyte- forming  organs, 
or  (2)  the  leucocytes  themselves,  or  (3)  the  liver,  as  the  prob- 
able sources  of  the  origin  of  antibodies.  As  to  the  liver,  I  now 
call  attention  to  the  fact  that  this  organ  is  the  seat  of  destruc- 
tion of  great  numbers  of  red  blood  corpuscles ;  and  that  its  fluids 
are  very  freely  supplied  with  leucocytes,  some  of  which  come  to 
it  directly  through  the  portal  vein  after  their  apparent  origin 
in  the  spleen.  It  has  even  been  suggested  (by  Sajous)  that  the 
eosinophiles  may  be  formed  in  the  liver. 

All  in  all,  it  may  fairly  be  said  that  the  experimental  evi- 
dence raises  at  least  a  strong  presumption  in  favor  of  the  belief 
that  the  lymphoid  tissues  that  develop  the  leucocytes,  and  the  leu- 
cocytes themselves,  are  closely  associated  *  with  the  processes 
through  which  certain  types  of  antibodies  are  developed.  The 
antibodies  in  question,  according  to  the  Proteomorphic  theory, 
are  the  "complement"  and  sundry  bactericides,  bacteriolysins, 
agglutinins,  opsonins,  and  precipitins — in  a  word,  the  antibodies 
evoked  by  antigens  composed  of  unbroken  proteins,  including, 
of  course,  the  bodies  of  living  and  dead  bacteria. 

If  the  direct  evidence  for  this  part  of  the  theory  is  not  abso- 
lutely demonstrative,  at  least  it  may  be  said  that  there  are  no 
experiments  that  clearly  contradict  it.  Meantime,  it  is  worth 
while  to  inquire  whether  the  general  relations  of  the  leucocyte 
and  its  parent  cells,  viewed  in  the  evolutionary  scale,  are  such 
as  to  justify  the  assumption  that  they  perform  the  particular 
functions  here  ascribed  to  them.  Such  a  discussion  could,  of 
course,  have  no  force  were  it  contradicted  by  direct  experimental 
evidence;  but  it  may  have  confirmatory  value  when  its  findings 
seem  to  accord  with  those  of  the  experimenters. 


56    THE  PROTEOMORPHIC  THEORY  AND  THE  NEW  MEDICINE 

THE  PRIMORDIAL  LEUCOCYTE 

In  such  a  view,  it  would  appear  that  the  leucocyte  is  a  rela- 
tively unspecialized  cell,  the  least-modified  present-day  repre- 
sentative of  the  prototypal  single-celled  ameboid  organism  from 
which  the  entire  body  has  developed.  It  is  consistent  with  this 
view  that  the  leucocyte  should  have  retained  the  primitive  func- 
tions of  digestion  and  assimilation  of  proteid  bodies  as  its  essen- 
tial task  in  the  developed  body. 

It  is  not  unlikely,  then,  that  in  reviewing  the  conditions  which 
determine  the  relations  of  the  protozoan  to  its  environment  we 
may  gain  an  insight  for  the  better  interpretation  of  some  of  the 
activities  of  the  leucocyte,  its  lineal  descendant. 

If,  then,  we  go  back  to  the  evolutionary  beginning,  and  review 
in  imagination  the  conditions  of  the  time  when  the  only  living 
organisms  were  single-celled  ones,  we  must  think  of  our  primor- 
dial ancestor  as  a  protoplasmic  cell  endowed  with  a  curious  ca- 
pacity to  absorb  certain  materials  from  the  environment,  and 
through  assimilating  them  to  grow ;  endowed,  also,  in  the  pur- 
suance of  this  mission,  with  capacity  to  respond  to  impressions 
received  from  the  environment. 

The  protoplasm  making  up  the  body  of  this  primitive  organism 
was  a  compound  of  carbon,  hydrogen,  oxygen,  and  nitrogen,  with 
minute  quantities  of  a  few  other  chemicals,  notably  sulphur; 
which  was  liquid  in  character,  but  differed  in  its  essential  qual- 
ities from  the  inorganic  substances  about  it,  chiefly,  we  may 
suppose,  because  of  the  exceedingly  intricate  character  of  the 
relations  of  the  very  large  number  of  atoms  that  entered  into 
each  molecule.  The  physical  principles  that  determined  the  rela- 
tions of  this  protoplasmic  solution  with  other  solutions  in  which 
it  might  be  immersed  were  determined  in  accordance  with  the 
laws  of  capillary  absorption  and  of  osmosis. 

The  essential  functions  of  the  protoplasm,  in  virtue  of  which 
it  might  be  spoken  of  as  a  living  organism,  were  probably  con- 
tingent on  the  fact  that  each  molecule  contained  a  large  num- 
ber of  atoms  of  carbon,  an  element  having  four  chemical  valences ; 
and  a  considerable  number  of  atoms  of  nitrogen,  an  element 
that  may  have  either  three  or  five  valences,  and  which  is  signally 
characterized  by  its  unwillingness  to  enter  into  combination,  and, 
contrariwise,  its  exceeding  desire  for  liberty  when  once  it  has 
been  combined,  resulting  in  the  instability  of  all  nitrogen  com- 
pounds. Nearly  all  explosive  compounds,  it  may  be  noted,  con- 
tain a  nitrogen  element.  Indeed,  the  analogy  as  to  composition, 
between  protoplasm  and  dynamite  and  other  high  explosives,  is 
striking  and  highly  suggestive.  There  is  one  important  differ- 
ence, however — artificial  explosives  contain  enough  oxygen  to 


MECHANISM    OF   PROTEIN    HYDROLYSIS   AND   IMMUNIZATION       57 

burn  their  other  constituents;  whereas  the  protein  molecule,  in 
order  that  it  may  not  be  too  unstable,  is  provided  with  a  com- 
paratively small  supply  of  oxygen. 

Recall  now  the  principles  of  osmosis,  as  revealed  by  the  studies 
of  Van't  HofT.  It  appears  that  osmosis,  or  the  passage  of  liquid 
through  a  membrane  from  one  solution  to  another,  is  due,  not 
to  any  suction  principle,  but  to  the  pressure  on  the  membrane 
exerted  by  the  molecules  of  the  denser  liquid;  that  is  to  say,  the 
liquid  which  has  the  larger  number  of  free  molecules  in  a  given 
volume. 

A  single  liberated  atom  or  ion  of  oxygen  or  any  other  element 
is  the  osmotic  equivalent  of  the  most  gigantic  protein  molecule. 

This  is  the  curious  fact  discovered  by  Van't  Hoff,  and  substan- 
tiated through  the  researches  of  Arrhenius  and  Ostwald.  It  is 
of  fundamental  importance  in  its  application  to  the  relations  of 
the  living  cell. 

Suppose,  for  example,  that  a  full-sized  protein  molecule  in  the 
protoplasm  of  a  living  cell  were  suddenly  to  be  disrupted  into 
molecules  of  its  component  substances,  the  amino-acids.  Imme- 
diately the  osmotic  pressure  exerted  by  the  molecule  would  be 
increased  a  hundred  fold.  The  pressure  might  disrupt  the  cell- 
Short  of  that,  it  would  result  in  pressing  the  cell  wall  outward 
against  the  surrounding  fluid,  with  the  result  that  a  certain 
amount  of  that  fluid  would  pass  through  the  cell  wall  and  be- 
come a  part  of  the  cell  content.  Suppose,  then,  just  as  equi- 
librium of  pressure  between  the  cell  and  its  surroundings  is  re- 
established, there  is  a  recombination  of  the  dissociated  elements 
to  produce  full-sized  protein  molecules.  A  hundred  or  so  amino- 
acid  molecules  becoming  a  single  protein  molecule,  the  osmotic 
pressure  in  the  cell  would  be  correspondingly  reduced,  with  the 
result  that  the  cell  would  contract  under  stress  of  outside  pres- 
sure and  exude  a  portion  of  its  content. 

It  is  not  unlikely  that  this  process  may  explain  the  enigmatic 
action  even  of  such  highly  developed  cells  as  the  muscle  cell  in 
the  animal  body,  the  contraction  of  which  has  never  been  clearly 
understood. 

I  am  not  unaware  that  some  physicists  have  denied  that  the 
laws  of  osmosis  apply  to  colloidal  substances.  But,  aside  from 
the  apriori  improbability  that  these  liquids  defy  the  operation  of 
so  fundamental  a  law,  the  balance  of  evidence  seems  corrobora- 
tive. And,  as  regards  the  particular  application  in  hand,  there 
is,  I  believe,  no  alternative  hypothesis  that  explains  muscular 
action  so  satisfactorily.  A  decompounded  molecule  of  muscle- 
cell  protein  becomes,  let  us  say,  one  hundred  molecule  of  amino- 
acids;  and  the  osmotic  pressure  within  the  cell  is  increased  a 
hundred  fold.  The  swelling  and  hardening  of  the  muscle,  with 


58      THE   PROTEOMORPHIC   THEORY   AND  THE    NEW    MEDICINE 

associated  contraction  due  to  the  arrangement  of  the  cells  in  the 
muscle-fiber  sheath,  is  the  tangible  aggregate  result.  When  the 
ammo-acid  molecules  are  recompounded  into  larger  protein 
molecules,  their  number  and  consequently  their  osmotic  pressure 
are  correspondingly  reduced,  and  the  muscle  relaxes. 

Whatever  the  force  of  this  parenthetical  suggestion,  however, 
it  is  certain  that  osmotic  action  explains  many  of  the  funda- 
mental processes  of  assimilation.  It  should  be  added,  however, 
that  in  a  comprehensive  view,  the  character  of  the  cell  wall  itself 
must  not  be  overlooked.  The  permeability  of  this  is  an  impor- 
tant consideration ;  and  it  has  been  found  that  the  nature  of  the 
medium  in  which  it  lies,  notably  with  reference  to  mineral  salts, 
may  greatly  modify  this  permeability.  At  the  moment,  however, 
this  aspect  of  the  subject  need  not  be  examined  in  detail. 

It  is  obvious  that  our  primitive  bit  of  protoplasm,  under  the 
shifting  conditions  of  osmosis,  expanding  and  contracting  as  por- 
tions of  its  protein  content  are  dissociated  and  re-formed,  may 
have  acquired,  by  virtue  of  this  principle  alone,  a  certain  function 
of  primitive  motion.  Granted  a  group  of  unstable  carbon-nitro- 
gen compounds  encased  in  a  cell  wall,  we  have  a  primitive  organ- 
ism which  may  manifest  the  fundamental  conditions  of  assimila- 
tion and  excretion. 

The  precise  chemical  composition  of  the  cell-content  making  up 
the  body  of  this  living  organism,  in  connection  with  its  funda- 
mental proteins,  will  depend  upon  the  chemical  composition  of 
the  medium  in  which  it  lives,  and  from  which  it  absorbs  matter, 
and  into  which  it  excretes  residual  matter.  And  in  any  case 
in  which  the  mechanism  of  absorption  and  excretion  of  a  given 
cell-laboratory  has  reached  a  status  of  equilibrium,  the  intrusion 
of  any  new  chemical  substance  into  the  medium  must  serve  as  a 
disturbing  element. 

Suppose  that  this  disturbing  element  takes  the  form  of  another 
organism,  which  has  been  accustomed  to  a  different  medium,  and 
hence  which  has  developed  a  somewhat  different  chemical  com- 
position, to  the  extent  at  least  of  modifying  the  side-chains  of  its 
protein  molecule.  Then,  in  the  nature  of  the  case,  there  must 
be  a  certain  antagonism  between  the  two  organisms.  Each, 
through  its  excretions,  modifies  somewhat  the  character  of  the 
medium,  and  makes  it  in  a  sense  an  abnormal  medium  for  the 
other.  Unless  both  organisms  are  able  to  modify  somewhat  their 
previous  mode  of  existence,  finding  a  way  either  to  assimilate 
or  to  neutralize  the  abnormal  elements  now  introduced  into  the 
medium,  they  cannot  survive. 

If  either  of  them  does  survive,  that  fact  is  proof  positive 
that  the  organism  in  question  has  found  a  way  to  adapt  itself 
to  the  new  conditions.  It  has  so  adjusted  and  modified  the 


MECHANISM    OF   PROTEIN    HYDROLYSIS   AND    IMMUNIZATION      59 

regular  routine  of  its  internal  chemical  processes,  that  the  excre- 
tions of  the  other  organisms  are  no  longer  noxious  to  it.  If  we 
choose,  we  may  say  that  the  organism  has  developed  autobodies 
or  antitoxins  against  the  offending  neighbor  organism.  Thus  it 
would  appear  that  the  production  of  such  antibodies  must  be 
one  of  the  most  fundamental  and  primordial  of  life  processes. 
It  is  a  function  that  is  retained  throughout  the  history  of  all 
descendants  of  the  protozoan,  even  to  the  remotest  cell  of  the 
highest  organism. 

The  reason  for  this  is  not  far  to  seek;  for  it  is  a  familiar 
axiom  of  the  evolutionist  that  all  life  is  a  struggle;  and  it  is 
obvious  that  the  developing  organism  must  come  constantly  in 
contact  with  other  organisms.  With  each  new  one,  the  old 
struggle  must  be  renewed  with  slightly  new  aspects,  and  new 
methods  must  be  found  to  equalize  the  adverse  conditions 
introduced. 

As  the  organism  evolves  to  a  multi-cellular  condition,  and  de- 
velops the  various  members  and  organs  that  mark  the  higher 
animals,  it  will  pass  constantly  to  new  environments  and  come 
in  contact  with  new  enemies.  Every  time  it  encounters  a  new 
type  of  food,  be  it  vegetable  or  animal,  it  will  present  a  new 
problem  to  its  chemical  laboratory  of  the  digestive  and  the 
assimilative  system.  And  unless  this  chemical  laboratory  proves 
adequate  to  the  new  task  put  upon  it,  the  organism  will  die. 

It  follows  that  every  existing  organism  has  been  able  to  run 
this  gauntlet  and  to  find  a  solution  of  the  new  problems  pre- 
sented to  it. 

In  other  words,  every  existing  organism  has  learned  to  digest 
and  assimilate  a  great  variety  of  proteins ;  developing  mechanisms 
for  neutralizing  their  poisons,  until  foods  that  were  toxic  have 
now  become  wholesome. 

In  this  view,  it  will  be  observed,  there  is  no  suggestion  that 
one  kind  of  protein  rather  than  another  is  poisonous.  It  is  simply 
that  each  specific  type  of  protein  is  somewhat  antagonistic  to 
organisms  composed  of  any  other  type  of  protein.  It  is  only  a 
cannibalistic  protein  diet  that  can  be  said  to  be  intrinsically  harm- 
less. But  cannibalism  involves  the  penalty  of  probable  race 
extinction ;  and  so  in  the  nature  of  things  evolutionary  all  living 
organisms  have  learned  to  feed  on  the  protein  of  other  races 
of  organisms,  adapting  their  own  metabolic  processes  until  they 
are  able  to  deal  effectively  with  the  offending  side-chains  in  the 
foreign  molecule.  Such  a  process  of  adaptation  requires  time, 
and  we  may  take  it  for  granted  that  foreign  proteins  are  "whole- 
some" to  any  given  organism  somewhat  in  proportion  to  the 
length  of  time  during  which  the  ancestors  of  that  organism  have 
been  accustomed  to  ingest  it.  That  any  given  protein  food  is 


60      THE   PROTEOMORPHIC   THEORY   AND  THE   NEW    MEDICINE 

observed  to  be  non-toxic  is  in  itself  proof  positive  that  the  organ- 
ism is  equipped  with  an  immunizing  mechanism  adapted  to  deal 
with  the  specific  minor  combinations  of  atoms  that  make  up  the 
side-chain  components  of  its  protein  molecules. 

Nor  does  this  apply  exclusively  to  the  proteins  that  we  com- 
monly think  of  as  foods.  It  has  equal  application  to  the  micro- 
scopic proteid  organisms.  Thus  bacteria  are  relatively  harmless 
if  they  are  so  abundant  that  the  organisms  of  our  ancestors  have 
dealt  with  them  generation  after  generation ;  contrariwise,  they 
are  classed  as  toxic  if  they  are  comparatively  rare,  so  that  the 
race  has  not  developed  a  defensive  mechanism  against  them. 
Note,  by  way  of  illustration,  that  measles  is  a  mild  disease  in 
Europe  and  America,  but  becomes  a  very  virulent  one  in  Japan. 
The  presumption  is  that  the  germ  of  measles  did  not  come  in 
contact  with  the  ancestors  of  our  race  until  a  period  subsequent 
to  that  in  which  the  Japanese  stock  had  branched  from  the 
western  stock. 

There  is  abundant  evidence  to  show  that  any  inherent  habit 
of  action  once  fixed  on  a  living  organism  is  a  perpetual  endow- 
ment, to  be  transmitted  from  one  generation  to  another  in  per- 
petuity (subject,  in  case  of  recently  acquired  characters,  to  elim- 
ination in  a  certain  proportion  of  the  progeny  through  Mundelian 
inheritance).  So  we  may  safely  assume  that  when  an  organism 
has  learned  to  deal  with  any  given  protein  in  such  a  way  as  to 
render  it  innocuous,  the  descendants  of  that  organism  will  retain 
the  capacity  to  repeat  the  process  indefinitely.  It  follows  that 
every  higher  organism  can  deal  effectively — under  proper  condi- 
tions and  in  restricted  quantities — with  all  the  different  types  of 
proteins  that  have  come  in  regular  contact  with  its  ancestors  to 
the  remotest  generations. 

Thus  is  explained  the  familiar  fact  that  each  higher  organism 
can  find  nourishment  in  a  great  variety  of  foods ;  coupled  with 
the  fact  that  the  blood  plasma  of  the  organism  normally  con- 
tains the  antidotes  for  a  considerable  number  of  bacterial  poisons. 

Of  course  this  higher  organism  has  become  a  very  complex 
mechanism,  with  many  members,  each  specialized  to  perform  a 
particular  function.  As  regards  this  function  of  combating  the 
noxious  forces  of  the  environment,  the  digestive  system  is  pre- 
eminent. But  this  system,  in  the  broad  view,  is  not  so  much 
an  inherent  part  of  the  organism,  as  an  outer  wall  of  defense  so 
placed  as  to  make  sure  that  in  general  no  unmodified  proteins  shall 
find  their  way  through  the  mucous  membrane  fortifications.  But 
the  organism  cannot  depend  absolutely  on  this  defensive  mech- 
anism, as  we  have  just  seen ;  so  it  is  necessary  to  have  other 
defenders  on  guard  inside  the  walls.  And  it  seems  on  its  face 
a  plausible  suggestion  that  the  cell  which  retains  most  of  the 


MECHANISM   OF  PROTEIN    HYDROLYSIS  AND   IMMUNIZATION      61 

character  of  the  primitive  primordial  protozoal  ancestor,  and 
which,  so  far  as  we  can  see,  is  not  specialized  to  perform  any 
other  function,  is  the  one  which  has  retained  pre-eminently  this 
primordial  capacity  of  harmonizing  the  organism  with  the  living, 
or,  once  living,  elements  of  its  environment. 

Such  a  primitive  cell  is  found  in  the  leucocyte.  No  other  cell 
in  the  body  retains  so  fully  the  primitive  characteristics  of  the 
protozoal  ancestor.  And,  patroling  everywhere  the  blood  stream 
which  carries  particles  ingested  from  the  outer  world,  the  leuco- 
cyte is  most  favorably  situated  to  come  immediately  into  contact 
with  intruding  substances,  and  to  take  up  with  the  least  pos- 
sible loss  of  time  the  work  of  so  modifying  them  that  they  meet 
the  needs  of  the  organism. 

The  leucocyte  looks  like  an  ameba,  and  it  is  seen  to  ingest 
solid  particles  of  food  just  as  an  ameba  does.  Can  we  doubt  that 
its  chemical  processes  of  digestion  are  closely  comparable  to  those 
of  its  prototype? 

THE  LEUCOCYTE  AS  A  MICROCOSM 

At  the  first  thought,  it  might  seem  to  strain  probabilities  to 
the  breaking  point  to  suggest  that  a  cell  of  such  proportions  as 
the  leucocyte  could  conceivably  be  the  habitat  of  a  series  of  chem- 
ical substances  so  complex  and  varied  as  is  here  implied.  But 
a  very  brief  consideration  of  the  facts  as  to  the  size  of  mole- 
cules and  atoms,  as  placed  at  our  disposal  by  the  modern  physicist, 
dispels  any  such  doubts. 

It  is  known  that  the  smallest  particle  visible  under  the  micro- 
scope is  about  one  fifty-thousandth  of  a  centimeter  in  diameter. 
Cubing  this  number,  we  find  that  a  cubic  centimeter  will  contain 
one  hundred  and  twenty-five  thousand  billions  of  such  particles. 
But  the  researches  of  Rutherford,  who  has  somewhat  accurately 
determined  the  size  of  the  atom,  show  that  a  cubic  centimeter 
of  space  may  contain  twenty  billion  times  that  number  of  helium 
atoms. 

In  other  words,  the  smallest  particle  visible  under  the  micro- 
scope is  large  enough  to  contain  many  times  twenty  billion  atoms  ; 
inasmuch  as  the  atoms  computed  by  Rutherford  were  in  the  gas- 
eous condition,  and  hence  very  much  more  widely  separated  than 
those  in  the  solid  particle  under  the  microscope. 

It  appears,  then,  that  if  we  were  to  assume  that  there  are  one 
thousand  different  antibodies  developed  in  the  organism — each 
one  antagonistic  to  some  specific  type  of  protein — there  is  ample 
opportunity  for  such  a  collection  of  antibodies  in  the  smallest 
particle  of  matter  visible  under  the  microscope,  even  if  we  assume 
that  each  one  of  these  antibodies  is  made  up  of  at  least  twenty 


62      THE   PROTEOMORPHIC  THEORY   AND  THE    NEW    MEDICINE 

million  atoms.  So  even  if  the  leucocyte  were  far  smaller  than 
it  is  (for,  of  course,  it  is  by  no  means  at  the  limit  of  microscopic 
visibility),  its  nucleus  might  be  a  very  intricate  structure  indeed, 
chemically  considered — a  chemical  laboratory  quite  elaborate 
enough  to  generate  all  the  different  types  of  antibody  that  the 
system  could  conceivably  require. 

Each  of  these  nascent  antibodies,  as  lodged  in  the  leucocyte, 
may  be  supposed  to  represent  a  specific  protein,  capable  of  taking 
to  itself  the  right  combination  of  atoms  to  increase  in  size  and, 
under  proper  conditions,  to  multiply  indefinitely,  to  meet  the 
needs  imposed  by  the  intrusion  of  a  particular  type  of  toxic  pro- 
tein. In  the  ordinary  course  of  events,  doubtless,  only  a  compara- 
tively small  number  of  the  different  types  of  antibodies  in  the 
equipment  of  the  leucocyte  laboratory  would  be  called  upon  to 
come  into  action  at  a  given  time.  It  might  even  happen  that 
for  long  periods  of  time,  even  for  generations,  a  particular  type 
of  nascent  antibody  that  has  been  developed  in  the  cell  might 
not  be  called  upon  to  meet  and  antagonize  its  specific  antigen. 

But  what  we  know  of  the  germ-cell,  and  of  the  possible  qui- 
escence of  hereditary  factors  for  successive  generations,  teaches 
us  that  it  may  readily  be  possible  for  the  cell  to  carry  forward 
during  an  indefinite  period  such  unused  increments  of  nascent 
antidotes ;  and  yet  to  call  them  into  action  when  the  proper  stim- 
ulus comes,  even  though  such  stimulus  has  not  hitherto  been 
applied  for  many  human  generations. 

In  this  view,  then,  we  may  think  of  the  cells  that  generate  the 
leucocyte  as  a  storehouse  in  which  minute  quantities  of  large 
numbers  of  different  types  of  proteins  are  arranged,  in  what 
may  be  called  the  nascent  state,  all  of  them  with  potentialities  of 
development,  and  a  certain  number  of  them  constantly  called 
upon  to  meet  the  stimulus  of  external  conditions  in  the  form  of 
different  types  of  protoplasms  or  proteids  that,  but  for  their  aid, 
would  be  poisonous  to  the  organism  in  the  blood  stream  of  which 
their  daughter  cells,  the  leucocyte,  are  liberated. 

It  is,  of  course,  the  mother  cells,  in  bone  marrow  and  spleen 
and  lymph  node,  that  must  be  thought  of  as  the  permanent  source 
of  supply  of  these  nascent  antibodies.  For,  of  course,  the  devel- 
oped leucocyte,  once  it  has  gone  out  from  the  parental  abode,  is 
in  a  sense  an  independent  organism,  lying  beyond  the  bounds  of 
the  cellular  system  of  the  complex  organism  in  the  blood  stream 
of  which  it  operates.  The  force  of  this  view  is  very  well  illus- 
trated in  the  familiar  fact  that  when  toxic  bacteria  are  ingested 
by  a  phagocytic  leucocyte,  these  toxic  bacteria  are  no  longer  able 
to  exert  a  malignant  influence  on  the  organism.  For  a  time  they 
retain  their  normal  form  and  appearance ;  but  the  leucocyte,  by 


MECHANISM   OF   PROTEIN    HYDROLYSIS  AND   IMMUNIZATION      63 

engulfing  the  intruder,  has  given  entire  protection  to  its  human 
host. 

Let  it  be  further  recalled  that  this  probably  would  not  be  true 
of  any  cells  other  than  the  leucocytes  in  the  entire  organism. 

This  fact,  taken  by  itself,  gives  strong  corroboration  to  the 
thought  that  the  leucocyte  is  primarily  and  fundamentally  a  de- 
tached organism,  acting  in  close  alliance  with  the  animal  body,  but 
being  in  a  broad  sense  independent. 

Of  course,  the  same  line  of  reasoning  applies  in  considerable 
measure  to  the  red  corpuscles  as  well.  And,  in  both  instances, 
the  general  idea  under  consideration  finds  strong  support  in  the 
fact  that  the  blood  corpuscles  of  different  mammals  are  histo- 
logically  so  similar  as  to  appear  practically  identical  under  the 
microscope.  Place  a  drop  of  guinea-pig's  blood,  for  example, 
and  a  drop  of  human  blood,  under  the  microscope,  and  not  even 
the  trained  hematologist  can  distinguish  one  set  of  corpuscles 
from  the  other.  Even  as  regards  the  numerical  count,  there  is 
striking  similarity  in  case  of  the  red  corpuscles ;  and  the  modi- 
fications in  leucocyte  count,  aggregate  and  differential,  are  such 
as  may  readily  be  accounted  for  by  long-established  minor  differ- 
ence of  dietetic  habits — modifications,  moreover,  that  may  be 
brought  into  strict  conformity  by  fluctuations  in  the  human  leuco- 
cyte count  under  conditions  of  slight  abnormality. 

Obviously,  such  conformity  of  corpuscular  population  in  the 
blood  of  mammals  widely  separated  in  the  evolutionary  scale, 
suggests  functions  of  very  general  and  fundamental  character, 
responsive  to  environmental  conditions  universally  distributed — 
for  example,  foodstuffs  substantially  the  same,  and  bacterial  in- 
vaders absolutely  identical. 

In  this  comprehensive  view,  then,  we  shall  do  well  to  get 
away  from  the  notion  of  virulent  bacteria,  and  to  think  of  all 
the  stages  of  assimilation  and  immunization  as  closely  allied, 
and  as  applying  to  proteins  in  general.  In  practice  we  must 
recognize  the  virulence  of  certain  types  of  bacteria;  but  we 
shall  do  well  to  understand  this  virulence  as  conditioned  merely 
on  the  fact  that  the  organism  has  come  somewhat  rarely  in  con- 
tact with  these  particular  microbes.  There  are  myriads  of  bac- 
teria always  in  the  organism  and  these  for  the  most  part  are 
as  innocuous  as  flecks  of  albumin,  for  the  simple  reason  that 
they  have  been  so  long  with  us  that  they  have  become  domesti- 
cated— that  is  to  say,  the  body-tissues  have  become  immunized 
against  them. 

According  to  the  Proteomorphic  theory,  as  we  have  seen,  such 
immunization  has  resulted  in  part  from  the  activities  of  the 
leucocyte,  through  which  the  blood  plasma  has  come  to  be  con- 
stantly permeated  with  antidotal  chemicals. 


64    THE  PROTEOMORPHIC  THEORY  AND  THE  NEW  MEDICINE 

ANTITOXINS  AND  NEW  CHEMICAL  PROBLEMS 

There  are  certain  types  of  these  antidotal  chemicals,  however, 
to  which  we  have  hitherto  given  scant  attention.  These  are  the 
so-called  antitoxins  which  are  developed  in  the  blood  not  neces- 
sarily because  of  the  presence  of  proteid  bodies,  but  in  response 
to  toxins  that  are  themselves  the  product  of  protoplasmic  activ- 
ity. No  organism  can  grow  and  develop  without  giving  out  waste 
products  that  are  poisonous  to  living  protoplasm ;  and  the  bac- 
terium is  no  exception  to  the  rule.  So  when  it  finds  access  to 
the  human  system,  it  necessarily  vitiates  that  system  with  its 
waste  products. 

We  ordinarily  think  of  these  as  toxic  properties  that  are  put 
out  by  the  bacteria  with  the  express  design  of  injuring  the  human 
body.  But  such  a  view  is  altogether  anthropomorphic  and  mis- 
taken. The  so-called  toxins  are  merely  either  (1)  waste  prod- 
ucts, or  (2)  enzymes  put  forth  by  the  bacteria  to  aid  its  own 
digestive  processes.  But  they  may  serve  as  virulent  poisons  to 
the  tissues  of  their  host  nevertheless — which  is  highly  unfor- 
tunate for  the  bacteria  themselves,  since  death  of  their  host  will 
in  many  cases  mean  death  for  them  also. 

Of  course,  the  bacteria  that  are  being  digested  by  the  leuco- 
cyte give  out  such  toxic  principles,  and  it  is  necessary  in  over- 
coming them  to  neutralize  these  toxins  as  well  as  to  proteolize 
the  body  of  the  bacterium  itself.  In  this  case,  we  may  suppose, 
the  leucocyte  adds  antitoxins  to  its  list  of  responsive  enzymes, 
along  with  the  antibodies  directly  aimed  against  the  proteid  bodies 
of  the  enemy.  It  is  possible  that  opsonin  is  such  an  antitoxin. 

But  there  are  also  cases  in  which  the  bacteria  only  lodge  on 
some  surface  of  the  body — say  the  throat — and  use  the  vascular 
channels  as  a  sort  of  sewer  into  which  to  discharge  their  waste 
products.  The  local  injury  may  be  very  slight,  the  entire  danger 
to  the  organism  resulting  from  the  presence  of  the  excretory 
toxins,  not  to  protein  itself  of  any  type.  The  colonization  of  the 
diphtheria  bacillus  furnishes  a  typical  illustration  in  point. 

In  such  a  case,  as  is  well  known,  the  body  may  be  able  to 
produce  chemicals  that  neutralize  the  toxins,  thus  saving  the  life 
of  the  human  organism.  Moreover,  these  chemicals  may  be  pro- 
duced in  such  excess  that  the  blood  becomes  more  or  less  satu- 
rated with  them,  giving  the  organism  immunity  to  similar  attacks 
in  the  future,  at  least  for  a  time.  These  neutralizing  chemicals 
are  known  as  antitoxins.  They  are  not  necessarily  poisonous 
to  the  bacteria  the  toxin  of  which  led  to  their  development.  The 
diphtheria  bacillus,  for  example,  will  grow  and  thrive  in  a  me- 
dium containing  large  quantities  of  diphtheria  antitoxin. 

Here,  then,  is  a  type  of  antibody  that  has  not  been  developed 


MECHANISM   OF  PROTEIN   HYDROLYSIS  AND  IMMUNIZATION      65 

directly  through  the  parenteral  presence  of  a  protoplasmic  body. 
And  the  question  at  once  arises  as  to  the  source  of  this  anti- 
toxin. Is  the  leucocyte  here  as  before  the  agent  that  guards 
the  body  from  the  insidious  attack? 

The  attempt  to  answer  this  question  has  proved  more  puzzling, 
if  possible,  than  the  attempt  to  localize  the  mechanisms  that  an- 
tagonize and  give  immunity  to  the  bodies  of  the  bacteria  them- 
selves. Most  workers  in  the  field  leave  the  question  quite  unan- 
swered. It  suffices  for  them  that  the  antitoxin  is  produced  some- 
where in  the  body,  and  that  it  ultimately  permeates  the  serum 
of  the  blood.  But  it  is  obvious  that  a  satisfactory  theory  of 
immunity  must  give  us  a  far  more  definite  answer. 

In  the  opinion  of  the  present  writer,  there  are  data  at  hand 
that  enable  one  to  answer  the  question  with  a  fair  degree  of 
definiteness.  It  must  be  admitted,  however,  that  these  data  do 
not  include  unequivocal  and  demonstrative  experiments,  such 
for  example  as  the  discovery  of  the  antitoxin  in  some  specific 
tissues  before  it  appeared  in  the  blood  serum.  We  must  be 
content  with  indirect  evidence.  This,  however,  is  to  say  the 
least  highly  suggestive,  and  its  findings  are  full  of  interest.  In 
my  opinion,  they  justify  the  belief  that  the  chief  agents  in  the 
formation  of  antitoxins  are  the  red  blood  corpuscles ;  their  efforts 
being  supplemented,  however,  on  occasion,  by  the  work  of  the 
leucocytes  on  one  hand  and  by  the  various  body  tissues  on  the 
other. 

The  evidence  is  based  very  largely  on  experiments  undertaken 
for  a  quite  different  purpose  and  having  to  do  with  the  hydrolysis 
and  synthesis  of  proteids.  In  particular  the  work  of  Emil  Fischer 
and  his  pupils  has  given  the  clue,  although,  so  far  as  I  am  aware, 
no  one  had  attempted  to  interpret  or  follow  it  up  until  this  was 
done  in  my  original  presentation  of  the  Proteomorphic  theory  in 
American  Medicine  of  October  and  November,  1914. 

To  gain  an  inkling  of  the  import  of  this  work,  in  the  present 
connection,  we  must  very  briefly  summarize  some  of  its  impor- 
tant findings  as  to  proteolysis.  The  most  significant  of  these  ex- 
periments, from  the  present  standpoint,  are  those  in  which  Abder- 
halden  has  tested  the  capacity  of  enzymes  excerpted  from  differ- 
ent bodily  tissues  to  hydrolyze  various  synthetic  polypeptids.  The 
polypeptids  were  so  named  by  Fischer  to  indicate  their  relation- 
ship with  peptones.  It  is  believed  that  the  peptones  (as  hydro- 
lyzed  from  protein  through  the  medium  of  proteoses)  consist 
of  a  chemical  aggregation  of  various  polypeptids.  Stated  other- 
wise, polypeptids  would  result  from  the  cleavage  of  peptones; 
although  in  point  of  fact  those  experimented  with  were  syn- 
thesized in  the  laboratory  by  the  combination  of  various  amino- 
acids. 


66     THE   PROTEOMORPHIC  THEORY  AND  THE   NEW   MEDICINE 

The  simplest  polypeptids  (di-peptids)  result  from  the  union 
of  two  amino-acids;  more  complex  ones  from  the  combination 
of  three  or  four  or  five  amino-acids.  The  molecule  of  a  poly- 
peptid  is,  therefore,  complex  as  compared  with  the  molecule  of 
an  amino-acid ;  but,  on  the  other  hand,  it  is  relatively  simple  as 
compared  with  the  molecule  of  peptone.  In  other  words,  a  mole- 
cule of  peptone  could  be  cleaved,  perhaps  by  successive  stages, 
to  form  a  goodly  number  of  molecules  of  the  most  complex  poly- 
peptids yet  synthesized. 

It  is  important  to  get  clearly  in  mind  this  position  of  the  poly- 
peptids as  nitrogenous  compounds,  which  are  considerably  more 
complex  than  amino-acids,  and  yet  very  simple  indeed  as  com- 
pared even  with  peptones,  which  in  turn  have  but  a  fraction  of 
the  complexity  of  the  original  protein  from  which  they  are  hydro- 
lyzed.  There  are  some  thousands  of  atoms  in  a  molecule  of  pro- 
tein ;  some  hundreds  in  a  molecule  of  peptone ;  some  scores  in  a 
molecule  of  the  more  complex  polypeptids ;  and,  as  we  have 
seen,  less  than  two  dozen  in  the  molecule  of  an  average  amino- 
acid. 

It  is  familiarly  known  that  the  giant  protein  molecule  which 
comes  into  the  stomach  as  the  chief  constituent  of  proteid  foods 
is  hydrolyzed  and  disintegrated  to  the  peptone  stage  (via  pro- 
teoses)  by  the  enzymes  of  the  digestive  tract.  Just  what  happens 
to  the  peptone  after  it  is  absorbed  into  the  intestinal  wall  has 
been  a  matter  of  dispute.  There  is  no  question  that  it  is  further 
metamorphosed,  for  it  does  not  appear  as  peptone  under  normal 
conditions  in  the  blood  stream.  The  balance  of  authority  lends 
strong  support  to  the  belief  that  the  peptone  is  further  hydro- 
lyzed in  the  intestinal  wall,  until  its  molecules  reach  or  approx- 
imate a  degree  of  smallness  that  makes  them  available  for  the 
use  of  the  various  body-cells  to  which  they  will  presently  be 
carried  by  the  blood  stream.  It  seems  highly  probable  that  they 
enter  the  blood  as  amino-acids,  of  various  types,  and  are  thus 
carried  to  the  tissues  as  dispensers  of  building  materials,  among 
which  each  individual  type  of  cell  may  select  in  accordance  with 
its  needs — for  the  different  body  proteins  are  made  up  of  dif- 
ferent combinations  of  amino-acids. 

But  we  have  seen  in  our  earlier  discussions  that  it  happens  on 
occasion  that  portions  of  the  proteins  taken  into  the  stomach 
find  their  way  through  the  intestinal  wall  unmodified,  or  not 
greatly  modified,  by  the  digestive  ferments,  and  introduce  a  com- 
plication in  the  problem  of  assimilation ;  a  complication  which, 
according  to  our  thesis,  is  met  by  the  activities  of  the  leucocyte. 
If  the  gigantic  molecule  of  protein  thus  finds  its  way  on  occa- 
sion through  the  intestinal  wall,  it  seems  plausible  to  suppose 
that  the  comparatively  small  molecules  of  the  polypeptid  order 


MECHANISM   OF  PROTEIN    HYDROLYSIS  AND   IMMUNIZATION      67 

must  make  similar  entrance  into  the  blood  stream  even  more 
frequently.  But  if  such  is  the  case,  we  may  fairly  assume  that 
means  will  be  found  there  to  effect  further  hydrolyses  in  the 
fluids  of  the  body.  And,  in  point  of  fact,  experiments  have 
shown  that  when  certain  polypeptids  are  artificially  introduced 
into  the  blood  stream  of  animals,  they  may  fail  to  appear  in 
the  excretions,  proving  that  they  have  been  metamorphosed  in 
the  body.  Abderhalden  found  that  a  considerable  number  of  the 
polypeptids  might  thus  be  utilized  by  the  organism  of  a  dog. 

Obviously,  then,  there  may  be  developed  within  the  body  tis- 
sues or  in  the  blood  stream  enzymes  capable  of  hydrolyzing  the 
polypeptid  molecule — a  molecule,  be  it  understood,  which  the 
combined  juices  of  the  stomach  and  pancreas  and  duodenum, 
under  ordinary  circumstances,  are  unable  completely  to  cleave 
or  break  down. 

The  interesting  question  arises  as  to  what  particular  tissue  or 
tissues  of  the  body  accomplish  this  remarkable  feat. 

Abderhalden  set  himself  the  task  of  experimentally  answering 
this  question.  In  conjunction  with  Pernuchi,  Hunter,  and  Rona, 
he  prepared  extracts  and  juices  of  various  organs,  using  Buch- 
ner's  method  of  grinding  up  with  sand  and  expressing  the  juices 
under  a  pressure  of  one  hundred  to  three  hundred  atmospheres, 
by  which  method  the  cell  enzymes  are  obtained.  The  tissues 
thus  treated  included  the  liver,  the  kidney,  and  the  muscles  of 
rabbits  and  dogs ;  lenses  from  the  eyes  of  pigs ;  the  brain  of  the 
calf;  blood  serum  of  ox,  rabbit,  and  dog;  and  blood  corpuscles 
of  various  types.  Different  types  of  polypeptids  were  used,  to 
test  the  selective  affinities  of  the  various  enzymes. 

It  was  found  that  the  juices  of  each  and  all  of  the  tissues 
just  named  (as  also  juices  of  germinating  wheat,  germinating 
lupine,  the  mushroom,  and  various  moulds)  contain  enzymes  that 
hydrolyze  one  or  another  of  the  polypeptids;  each  juice,  as  a 
rule,  acting  on  several  different  types  of  polypeptids.  Juices  of 
liver,  kidney,  and  muscle  hydrolyzed  the  simpler  polypeptids.  The 
plasma  and  serum  of  the  blood  both  hydrolyzed  complex  types  of 
polypeptids,  which  are  known  not  to  be  attacked  by  trypsin, 
proving  that  the  blood  fluids  did  not  receive  their  enzymes  by 
absorption  from  the  intestinal  tract. 

But,  in  any  event,  it  was  needless  to  look  far  afield  for  the 
origin  of  the  enzymes  in  the  blood  fluids,  inasmuch  as  the  juices 
expressed  from  the  red  blood  corpuscles  proved  capable  of  hydro- 
lyzing the  most  complex  polypeptids. 

The  leucocytes  of  a  horse,  on  the  other  hand,  failed  to  hydro- 
lyze a  polypeptid  which  the  red  blood  corpuscles  of  the  horse, 
and  also  the  blood  platelets,  hydrolyzed  actively.  -Blood  plate- 


68     THE   PROTEOMORPHlC  THEORY  AND  THE   NEW   MEDICINE 

lets,  there  is  reason  to  believe,  are  only  extruded  contents  of  red 
corpuscles. 

It  may  fairly  be  concluded,  then,  that  the  hydrolyzing  of  poly- 
peptids  that  find  their  way  into  the  blood  stream  may  be  accom- 
plished by  enzymes  secreted  by  various  organs  and  tissues,  includ- 
ing the  muscles;  that  the  red  blood  corpuscles  are  very  active 
agents  in  this  capacity,  notably,  perhaps,  with  regard  to  the 
most  complex  polypeptids ;  and  that  it  does  not  fall  within  the 
range  of  the  activities  of  the  leucocyte  to  deal  with  these  com- 
paratively simple  nitrogen  compounds.  The  leucocyte,  like  the 
organs  that  produce  the  digestive  ferment  of  the  intestine,  acts 
on  the  full-sized  protein  molecule,  and  begins  its  cleavage.  But 
in  the  light  of  the  new  evidence,  it  may  somewhat  be  doubted 
whether  the  leucocyte  is  able  to  carry  on  this  cleavage  to  its 
final  conclusion.  It  is  at  least  possible  that  the  protein  molecules, 
multiplied  by  cleavage,  acquired  an  osmotic  pressure  that  causes 
the  disruption  of  the  leucocyte  when  the  polypeptid  stage  of  hy- 
drolysis has  been  reached.  If  such  is  the  case,  the  autolyzed 
leucocyte  would  discharge  its  contents  in  the  midst  of  myriads 
of  red  blood  corpuscles  capable  of  taking  up  the  work  of  hydro- 
lysis where  the  leucocyte  left  it,  and  completing  the  cleavage  of 
polypeptids  into  amino-acids. 

According  to  the  hypothesis  already  expounded,  it  would  be 
only  comparatively  small  quantities  of  foreign  protein  that  would 
thus  come  under  the  auspices  of  the  leucocyte ;  but  it  is  not  un- 
likely that  considerable  quantities  of  polypeptids  may  find  their 
way  habitually  into  the  blood  stream ;  and  it  is  to  be  recalled 
that  the  red  corpuscles,  marshaled  in  numbers  not  far  from  a 
thousand  times  as  great  as  the  number  of  leucocytes,  should  be 
able  to  deal  with  the  polypeptids  in  almost  any  quantity. 

It  is  even  conceivable  that  all  the  protein  foodstuffs  are  ab- 
sorbed in  this  state  (since  the  evidence  for  their  change  into 
amino-acids  in  the  intestinal  wall  is  not  quite  conclusive),  and 
normally  undergo  their  final  stages  of  hydrolysis  under  influence 
of  the  erythrocytic  enzymes ;  the  tissues  of  the  liver  and  brain 
and  muscle  standing  guard  meantime  in  the  background,  as  it 
were,  ready  to  attack  (each  within  the  limits  of  its  capacity) 
any  portions  of  polypeptids  that  escape  the  militant  army  of  red 
corpuscles.  The  numbers  and  aggregate  bulk  of  the  red  cor- 
puscles suggest  their  possible  capacity  to  accomplish  such  a  task. 

These  experiments,  then,  enable  us  to  form  a  more  complete 
and  more  satisfying  mental  picture  of  the  processes  of  digestion 
and  assimilation  than  has  ever  hitherto  been  possible.  We  shall 
be  able  to  fill  out  certain  gaps  in  the  picture  as  we  proceed,  ulti- 
mately presenting  at  least  a  suggestive  scheme  of  the  entire  cycle 
of  protein  metabolism  in  the  body. 


MECHANISM  OF  PROTEIN  HYDROLYSIS  AND  IMMUNIZATION    69 

NEW  EXPERIMENTAL  EVIDENCE 

The  above  exposition  of  the  theory  of  proteolytic  activities 
of  the  red  corpuscles  is  reproduced  precisely  as  it  was  presented 
in  the  original  exposition  of  the  Proteomorphic  Theory  in  Amer- 
ican Medicine  of  October,  1914.  It  will  be  obvious  that  the 
hitherto  unsuspected  function  thus  ascribed  to  the  red  corpuscles 
matches  in  importance,  if  its  validity  is  demonstrated,  the  function 
of  carrying  oxygen  to  the  tissues — each  being  absolutely  essen- 
tial to  the  life  of  the  individual.  The  subject  having  such  funda- 
mental importance,  then,  it  will  be  of  interest  to  cite  here  a 
series  of  experiments  made  about  two  years  later,  which  give 
strong  support  to  the  theory  of  erythrocytic  polypeptid  digestion. 

The  experiments  in  question  have  to  do  with  the  distribution 
of  the  residual  nitrogen  between  the  blood  cells  and  the  plasms, 
originally  published  in  the  Biochemische  Zeitschrift,  as  reported 
in  Physiological  Abstracts  (published  by  the  Physiological  Society 
of  Great  Britain  and  Ireland  with  the  co-operation  of  the  Amer- 
ican Physiological  Society)  in  the  tissue  of  October,  1916.  The 
experimenter  was  Dr.  Ivar  Bang.  The  abstract  is  as  follows: 

"The  residual  and  urea  nitrogen  in  the  blood  and  plasma  were 
determined  in  well-nourished  rabbits  before  and  after  a  seven- 
day  fast  during  which  no  water  was  given.  The  amino-acid  frac- 
tion was  represented  by  the  difference  between  the  residual  and 
urea  nitrogen.  In  accordance  with  the  findings  of  earlier  experi- 
ments, an  increase  in  residual  nitrogen  occurred  after  the  fast 
which  concerned  the  urea  fraction  only.  Before  the  fast  urea 
was  equally  distributed  between  the  cells  and  the  plasma,  while 
the  cells  were  richer  than  the  plasma  in  amino-acid;  these  rela- 
tions persisted  after  the  fast. 

"After  the  introduction  of  a  solution  containing  two  to  three 
grams  of  glycine  into  the  bowel,  there  was  an  increase  in  the 
residual  nitrogen  of  the  blood,  which  affected  the  amino-acid  frac- 
tion almost  exclusively.  The  increase  was  confined  to  the  plasma, 
and  hence  the  amino-acid  content  of  the  blood  cells  is  probably 
formed  in  the  cells  themselves." 

It  will  be  observed  that  "blood  cells"  as  a  whole  are  here 
referred  to,  with  no  specific  reference  to  the  red  cells.  But  the 
fact  that  the  latter  are  about  one  thousand  times  as  numerous  as 
the  leucocytes,  constituting  the  main  bulk  of  the  formed  matter 
of  blood,  makes  it  highly  probable  that  the  amino-acids  in  ques- 
tion were  contained  very  largely  at  any  rate  in  the  eryphrocytes. 

Such  experimental  proof  of  the  completion  of  protein  hydroly- 
sis in  the  corpuscles  is  interesting  from  a  theoretical  standpoint, 


70      THE   PROTEOMORPHIC  THEORY  AND  THE    NEW    MEDICINE 

but  doubly  so  from  the  practical  standpoint  of  the  physician  ad- 
ministering proteins  therapeutically.  There  remains  little  doubt 
that  the  red  corpuscles  are  an  essential  part  of  the  mechanism 
through  which  intruding  proteins  are  ultimately  reduced  to  innoc- 
uous amino-acids. 

It  becomes  necessary,  then,  to  watch  the  red  corpuscles  no  less 
than  the  white  ones  as  an  aid  to  the  interpretation  of  the  patient's 
progress.  Not  merely  their  numbers,  but  their  qualitative  condi- 
tions should  be  considered— the  presence  of  normoblasts,  megalo- 
blasts,  poikailocytes,  crenated  and  friable  cells,  and  the  like  should 
be  closely  observed,  as  giving  clues  to  the  regulation  of  dosage, 
a  change  of  frequency  of  administration,  or  a  modification  of  the 
type  of  proteal  employed. 

The  fact  that  the  proteals  produce  rapid  and  significant  modi- 
fications in  the  number  and  character  of  the  red  cells  has  been 
too  frequently  observed  to  be  matter  of  doubt. 

The  subject  has  obvious  importance,  from  the  standpoint  of 
the  practical  physician,  as  will  appear  when  we  take  up  the  ques- 
tion of  the  therapeutic  protein  response  in  later  chapters. 

THE  RED  CORPUSCLE  AS  MASTER  IMMUNIZER 

But  where,  it  will  naturally  be  asked,  is  the  point  of  contact 
between  this  scheme  of  polypeptid  digestion  and  the  develop- 
ment of  antitoxins? 

The  answer  is  this:  The  bacterial  toxins  that  evoke  the  re- 
sponsive antitoxins  are  products  of  protoplasmic  activities ;  and 
they  are  known  to  be  comparatively  simple  in  chemical  composi- 
tion, their  molecules  being  in  all  probability  of  the  same  order  of 
complexity  as  the  molecules  of  polypeptids.  It  is  a  fair  presump- 
tion that  the  bodily  enzymes  proved  to  act  on  the  polypeptids 
are  the  ones  that  act  also  on  these  allied  bacterial  toxins. 

If  the  inference  is  justified,  the  sources  of  the  antitoxins  are 
clearly  revealed :  They  are  the  cells  of  the  entire  body,  each  type 
having  a  selective  action  of  its  own;  and,  in  all  probability,  the 
red  blood  corpuscles  being  the  ones  that  have  the  most  general 
and  the  most  comprehensive  activities  in  this  connection. 

Now  it  is  obvious  that  so  bold  an  assumption  as  this  requires 
all  the  support  that  can  be  found  for  it  in  analogical  reasoning. 
Fortunately  there  are  several  lines  of  such  reasoning  that  supply 
confirmatory  evidence. 

Thus,  bearing  in  mind  the  nitrogenous  character  of  the  waste 
products  of  protoplasmic  action  in  the  animal  organism  (for 
example  urea,  with  the  formula  CH4N2),  we  are  justified  in 
assuming  that  the  toxic  principles  given  out  by  the  virulent  bac- 
teria are  not  altogether  dissimilar  nitrogenous  compounds.  This 


MECHANISM   OF  PROTEIN    HYDROLYSIS  AND  IMMUNIZATION      71 

assumption  is  strongly  supported  by  the  observed  similarity  of 
action  of  these  toxins  and  sundry  narcotic  drugs  of  the  familiar 
alkaloids.  And  these  alkaloids  have  known  chemical  formulae 
that  at  once  reveal  their  chemical  relationship  with  the  poly- 
peptids. 

Morphine,  for  example,  is  C17H19NO3 ;  strychnine  is 
C21H22N2O2 ;  and  glycyl-glycine,  the  simplest  of  the  polypeptids 
has  the  formula  C8H16N4O6.  If  we  knew  how  to  combine  the 
amino-acid  called  valine  (C^uNC^)  with  the  amino-acid  called 
leucine  (C6H13NO2),  we  should  have  a  molecule  with  the  compo- 
sition C11H24N2O4,  in  still  closer  simulation  of  the  strychnine 
molecule.  The  combination  of  two  molecules  of  the  amino-acid, 
glycine  with  one  of  leucine,  which  has  been  effected,  gives  the 
formula  C17H33N3O7. 

Of  course,  we  can  by  no  means  assume  that  because  the  com- 
binations of  atoms  in  a  given  pair  of  molecules  are  similar  the 
gross  physiological  effects  of  these  molecules  on  the  organism  will 
be  identical  or  even  comparable.  To  disprove  any  such  hypoth- 
esis, nothing  more  would  be  necessary  than  to  consider  the  chem- 
ical composition  of  certain  other  alkaloids,  for  example  quinine, 
which,  with  its  formula  C20H24N2O2  seems  to  have  close  touch 
with  strychnine ;  yet  which,  as  every  tyro  in  medicine  knows,  is 
very  fundamentally  different  in  its  physiological  action. 

It  should  be  understood,  however,  that  in  the  modern  view  a 
drug  acts  on  only  those  tissues  with  which  it  can  enter  into 
chemical  union ;  and  that  the  markedly  different  physiological 
actions  of  drugs  depends  upon  the  affinity  for  them  shown  by  this 
or  that  type  of  cell  in  the  tissues  of  the  body.  Quinine  and  strych- 
nine appear  to  us  radically  different  drugs,  because  their  effects 
on  the  human  system  are  so  conspicuously  diverse ;  yet  their 
chemical  composition  proves  their  close  similarity;  and  a  rea- 
sonable explanation  of  the  difference  in  their  effect  is  given  if 
we  assume  that  the  precise  combination  of  "side-chains"  in  the 
strychnine  molecule  chances  to  fit  in  with  the  scheme  of  the 
molecules  making  up  the  substance  of  the  central  tissue  of  the 
brain;  whereas  the  side-chains  of  the  quinine  will  link  it  with 
other  tissues  that  are  in  themselves  no  less  profoundly  affected 
than  are  the  brain  tissues  by  strychnine ;  but  which  are  not  so 
vitally  and  intimately  associated  with  the  life-processes  of  the 
organism  as  a  whole. 

It  is  in  the  fact  that  most  alkaloids,  in  common  with  toxins, 
find  their  affinities  in  the  cells  of  brain  and  spinal  cord  that  the 
seeming  toxicity  of  these  substances  lies.  Many  a  "harmless" 
compound  may  affect  muscle  cells,  let  us  say,  far  more  pro- 
foundly than  the  brain  cells  are  affected  by  morphine  or  strych- 
nine, yet  have  no  "toxic"  effect,  because  the  muscles  do  not 


72      THE   PROTEOMORPHIC   THEORY   AND  THE    NEW    MEDICINE 

contain  the  centers  of  cardiac  and  respiratory  control,  as  do  the 
nervous  centers. 

Considered  in  this  broad  way,  there  is  ample  justification  for 
the  belief  that  the  physiological  activities  of  all  drugs  are  inti- 
mately linked  with  their  chemical  composition ;  and  that,  in  the 
sense  just  interpreted,  drugs  of  closely  similar  chemical  compo- 
sition have  strictly  analogous  effects. 

But  everything  depends  upon  the  particular  tissue  cell  which 
chances  to  have  affinity  for  any  given  drug ;  and  the  experiments 
of  Abderhalden  as  already  cited,  showing  the  elective  affinities 
of  different  tissues  for  polypeptids,  may  be  considered  as  labora- 
tory interpretations  of  familiar  facts  of  clinical  medicine.  The 
fact  that  many  alkaloids  and  such  poisons  as  that  of  B.  tetanus, 
and,  indeed  most  of  the,  bacterial  toxins,  give  evidence  of  affecting 
the  brain,  dove-tails,  at  least  presumptively,  with  the  highly  inter- 
esting experiments  that  show  that  two  of  the  most  complex  of 
the  polypeptids  were  hydrolyzed  by  the  juices  expressed  from 
the  brain  cells  of  a  calf. 

It  may  be  added  that  in  the  case  of  two  less  complex  types  of 
polypeptids,  the  juices  of  the  calf-brain  failed  to  act;  and  con- 
ceivably it  is  not  stretching  analogies  too  far  if  we  observe  that 
the  alkaloids  which  are  known  to  have  a  pronounced  cerebral  effect 
are  considerably  more  complex,  particularly  as  regards  their  car- 
bon and  hydrogen  atoms,  than  the  simpler  (di-amino)  polypep- 
tids; and  if  we  associate  relative  complexity  of  molecular  struc- 
ture in  a  drug  with  affinity  for  the  cerebral  tissue,  in  itself 
presumably  the  most  complex  of  organic  bodies. 
.  Such  a  conception  must  be  held  with  great  reserve,  however, 
in  view  of  the  extraordinary  toxicity  of  the  simple  combinations 
CS2,  carbon  bisulphide,  and  HNC,  prussic  acid,  and  of  the  con- 
flicting evidence  elicited  by  observation  that,  whereas  nitriles  of 
the  fatty  series,  from  acetonitrile  to  isovaleronitrile,  increase  in 
toxicity  with  growing  molecular  weight,  substances  of  an  allied 
series,  starting  with  cyanacetic  methyl  ester,  C4HBHO2,  become 
less  toxic  (according  to  Berthe  and  Ferre)  with  increased  com- 
plexity, losing  toxicity  altogether  when  two  groups  of  C2H5O2  are 
inserted.  A  clue  will  perhaps  be  found  in  the  study  of  the 
valencies  of  the  nitrogen  atom,  which,  as  is  familiarly  known, 
is  either  trivalent  or  quinquevalent. 

SPECIFIC  AFFINITIES  AND  ANTAGONISMS 

Closely  in  keeping  with  these  rather  abstruse  theoretical  con- 
siderations are  the  familiar  and  very  practical  experiments  of 
Pasteur  through  which  the  anti-rabic  virus  was  developed.  Here, 
as  is  well  known,  the  material  used  for  making  the  protective 


MECHANISM   OF  PROTEIN    HYDROLYSIS  AND   IMMUNIZATION      73 

inoculation  is  found  in  the  spinal  cord  of  a  rabbit  that  has  been 
successively  inoculated  with  the  virus  of  rabies. 

Equally  suggestive  in  their  way  were  the  experiments  of  Was- 
sermann,  who  mixed  tetanus  toxin  with  the  brain  substance  of 
a  susceptible  guinea  pig  and  found  that  the  mixture  was  no  longer 
toxic  for  other  guinea  pigs.  This  seemed  to  show  a  special 
affinity  between  the  brain  substance  and  the  toxin,  inasmuch  as 
emulsions  of  other  organs  of  the  guinea  pig  when  brought  in 
contact  with  the  tetanus  toxin  exerted  no  such  effect.  "It  would 
appear  from  this  experiment,"  says  Nuttall,  "that  a  toxin  may 
have  a  special  affinity  for  special  tissue  cells,  and  this  appears 
to  explain  the  neuro-toxic  character  of  the  symptoms  which  are 
observed  in  tetanus." 

It  would  be  better,  perhaps,  to  say  that  certain  cells  have  an 
elective  affinity  for  the  toxin,  rather  than  to  make  the  converse 
statement;  best  of  all  to  think  of  the  attractions  as  mutual.  In 
chemical  terminology  some  cells  have  side-chain  groups  of  mole- 
cules for  which  the  molecules  of  the  toxin  can  readily  be  sub- 
stituted ;  or  with  which  they  may  be  combined  through  a  new 
arrangement  of  the  atoms.  What  determines  these  affinities  we 
shall  not  know  until  we  are  better  informed  as  to  the  ultimate 
nature  of  chemical  valences  in  general ;  but  for  the  present  pur- 
poses it  suffices  to  note  the  seeming  demonstration  that  such 
elective  affinities  exist,  and  that  they  are  exercised  by  various 
tissue  cells  of  the  body  in  connection  with  an  endless  variety 
of  nitrogen  compounds. 

Another  very  striking  illustration  of  such  elective  affinities, 
in  this  case  involving  the  muscle  cells  of  the  unstriped  muscles, 
is  furnished  by  the  amino-acid-like  product,  known  as  adrenalin. 

The  origin  of  this  product  in  the  supra-renal  glands,  and  its 
extraordinary  effect  in  constricting  arterioles,  are  familiar  to  the 
profession.  But  it  may  not  be  so  generally  known  that  adren- 
alin differs  by  only  two  hydrogen  atoms  in  chemical  composi- 
tion from  one  of  the  familiar  amino-acids  named  tyrosine.  Such, 
however,  is  the  fact,  the  formula  of  tyrosine  being  CgN^NOg, 
and  that  of  adrenalin  C9H13NO3.  That  adrenalin  exercises  its 
contractile  function  by  directly  influencing  the  muscle  fibers  of 
the  arterioles  is  shown  by  the  continuance  of  its  characteristic 
action  when  applied  locally  after  severance  of  the  nerves  leading 
to  the  tissue  under  treatment.  Let  it  be  observed,  too,  that  it  is 
the  cells  of  the  unstriped  muscles  alone  that  seize  on  the  adren- 
alin molecule;  the  cells  of  other  muscles  seeming  to  let  it  pass 
unnoticed. 

When  we  add  that  adrenalin  exists  normally  in  the  blood  only 
in  the  proportion  of  one  part  in  a  million,  yet  that  its  presence 


74      THE   PROTEOMORFHIC   THEORY  AND  THE    NEW    MEDICINE 

in  this  infinitesimal  quantity  seems  necessary  to  the  very  life  of 
the  organism,  light  is  thrown  from  yet  another  direction  on  the 
intricate  co-ordinations  of  the  animal  machine  as  effected  with 
the  aid  of  the  nitrogen-bearing  molecule. 

Here  is  a  substance  which,  were  we  able  to  remove  but  two 
of  its  hydrogen  atoms,  would  become  merely  a  commonplace 
member  of  the  group  of  amino-acids,  ready  to  be  taken  up  by 
this,  that,  or  the  other  tissues  of  the  body,  as  a  component  part 
of  its  protein ;  and  yet,  in  virtue  of  the  presence  of  those  two 
supernumerary  hydrogen  atoms,  it  gains  special  affinity  for  cells 
of  a  particular  type,  and  causes  those  cells,  in  recombining  their 
structural  materials,  to  undergo  a  destructive  metabolism  of 
an  almost  explosive  type  which  finds  'tangible  expression  in  a 
muscular  contraction. 

Could  we  look  into  the  structure  of  the  muscle  cells  during 
this  time  of  its  explosive  activity,  with  vision  more  ultra-micro- 
scopic than  is  afforded  by  any  instrument  yet  devised,  we  should 
see  that  the  cell,  in  readjusting  its  molecules,  has  some  left-over 
materials,  like  the  shavings  and  sawdust  of  a  carpenter,  that 
are  not  needed  in  the  new  combinations;  and  that  these  left- 
over products  are  excreted  into  the  surrounding  fluid  medium. 
And  what  is  true  of  the  muscle  cell  under  these  circumstances 
is  equally  true  of  every  other  muscle  cell  whenever  it  contracts 
from  whatever  cause,  and  of  the  cells  of  every  other  bodily  tissue 
when  they  undergo  characteristic  activities.  Changes  in  the  molec- 
ular structure  of  the  cell — incident  to  or  underlying  all  activity — 
are  affected  only  at  the  expense  of  potential  energy,  and  with 
actual  gain  or  lo'ss  of  physical  material.  Destructive  metamor- 
phoses, which  attend  the  active  functioning  of  all  tissues,  are 
attended  by  a  loss  of  substance.  And  it  is  almost  axiomatic  to 
say  that  the  precise  character  of  the  substance  given  out  as  a 
waste  product  or  a  by-product  must  be  dependent  on  the  char- 
acter of  the  substance  available  to  replace  it.  On  occasion  there 
comes  to  hand,  let  us  say,  a  group  of  atoms  that  is  admirably 
suited  to  fit  into  the  structure  of  the  molecule  of  the  cell,  pro- 
vided that  another  group  similar  in  character,  but,  on  the  whole, 
somewhat  less  satisfactory  is  excluded.  So  the  substitution  is 
made,  and  the  discarded  group  of  atoms  flows  away  in  the  blood 
stream. 

It  is  obvious  that  groups  of  atoms  that  can  thus  be  substituted 
one  for  the  other  may  bear  to  each  other  a  certain  complementary 
relation.  It  is  one  way  of  expressing  this  relation  to  say  that 
the  intruding  molecule  is  an  antigen,  and  that  the  extruded  one 
is  an  antibody.  In  view  of  the  mutual  relations  of  these  struc- 
tures, it  does  not  seem  strange  that  members  of  the  two  clans, 
when  they  chance  to  meet  in  the  blood  stream,  can  enter  into 


MECHANISM   OF  PROTEIN    HYDROLYSIS  AND   IMMUNIZATION      75 

mutual  combinations.  Two  groups  of  atoms' each  of  which  can 
unite  with  a  third  group  may  very  well  unite  with  each  other. 
But  when  the  antigen  has  thus  combined  with  an  antibody,  it 
no  longer  has  free  valences,  and  so  it  cannot  combine  with  the 
cell  that  it  formerly  would  have  entered.  In  the  event  that  the 
particular  antigen  in  question  was  the  kind  of  plotoplasmic  prod- 
uct that  we  call  a  toxin,  we  may  well  enough  call  the  antibody 
an  antitoxin ;  and  we  may  speak  of  the  union  of  the  two  as 
neutralizing  the  poison  and  rendering  it  harmless.  But  this,  of 
course,  applies  only  to  exceptional  instances  in  which  the  antigen 
had  properties  that  made  its  presence  objectionable  in  the  cell 
with  which  it  has  affinity.  Most  antigens  that  would  ordinarily 
be  found  in  the  body  have  not  such  harmful  properties,  and  their 
antibodies,  although  acting  in  the  same  way,  would  not  serve 
the  same  purpose. 

But  at  the  moment,  of  course,  I  have  specifically  in  mind  the 
antigens  that  are  toxic ;  and  their  specific  antibodies  are  the  anti- 
toxins. And  the  purport  of  the  present  phase  of  the  discus- 
sion is,  it  will  be  recalled,  to  make  it  seem  plausible,  on  various 
analogical  grounds,  that  each  and  every  living  cell  of  the  body 
must  on  occasion  take  to  itself  what  we  may  call  antigens,  and 
give  out  what  we  may  call  antibodies ;  and  that  the  particular 
tissues  that  can  produce  antibodies  in  response  to  any  given 
toxins  are  precisely  those  tissues  that  are  receptive  to  the  inva- 
sion of  that  toxin. 

If  the  toxin  be  one  for  which  the  brain  tissues  have  pre- 
eminent affinity,  the  antitoxin  produced  will  come  from  the  brain 
cells.  If  the  toxin  be  one  attacking  the  liver,  the  liver  cells 
will  furnish  the  antitoxin. 

However  specialized  any  cell  may  be  to  perform  pre-eminently 
a  particular  function  through  division  of  labor  in  the  entire  body 
every  cell  must  retain  the  primitive  capacity  to  take  in  nourish- 
ment and  give  out  excrementitious  products,  else  it  obviously 
could  not  maintain  existence.  And  it  is  conceived  that  the  pro- 
duction of  an  antitoxin  in  response  to  a  toxin  that  the  cell  can 
absorb  is  merely  a  special  manifestation  of  this  primal  and  funda- 
mental function. 

The  bacterial  toxins  are,  according  to  the  present  hypothesis, 
relatively  simple  nitrogen  compounds  of  a  type  suitable  for  com- 
bination with  various  of  the  body  cells — not  distantly  related  to 
the  amino-acids ;  the  production  of  complementary  bodies  or  anti- 
toxins by  these  body  cells,  under  these  conditions,  may  be  said 
to  be  a  commonplace  of  physiological  activity — though  sharing, 
of  course,  in  the  inscrutability  that  attaches  to  all  chemical 
processes. 


76      THE   PROTEOMORPHIC   THEORY   AND  THE   NEW    MEDICINE 

Loss  AND  GAIN  THROUGH  THE  DIVISION  OF  LABOR 

But  the  reader  who  would  clearly  apprehend  the  bearings  of 
the  theory  of  immunity  thus  exposited  must  on  no  account  fail 
to  note  the  exact  terms  of  this  definition  just  given.  The  anti- 
toxins, in  this  view,  are  produced  by  various  and  sundry  of 
the  body-cells,  because  these  antibodies  are  evoked  in  response 
to  the  coming  of  toxins  that  are  relatively  simple  nitrogenous 
compounds.  When,  however,  the  antigen  that  comes  is  not  a 
by-product  of  protoplasmic  activity,  but  the  protoplasm  itself 
as  evidenced  in  the  body  of  a  bacterium  or  in  molecules  of  un- 
broken protein  in  any  form,  the  case  is  quite  altered,  because  the 
body-cells  in  general  are  not  adapted  to  absorb  such  materials. 
Their  location  in  the  body,  shielded  by  encompassing  walls  of 
skin  and  mucous  membrane,  puts  them  out  of  contact  with  such 
crude  raw  materials,  the  transformation  of  which  has  been  turned 
over  to  an  especially  adapted  apparatus  known  as  the  digestive 
system. 

Each  cell  must  retain  the  capacity  to  take  food ;  but  it  may 
have  lost  the  capacity  to  imbibe  this  food  in  a  crude  or  undi- 
gested form. 

Such  is  indeed  the  condition  of  the  specialized  cells  of  the  brain 
and  muscles  and  of  the  parenteral  organs  in  general.  The  pen- 
alty of  their  specialization  is  that  each  of  them,  while  gaining  in 
one  feature,  has  lost  in  various  others.  The  single  speck  of 
protoplasm  that  constituted  the  entire  structure  of  the  primor- 
dial protozoal  ancestor  was  at  once  stomach  and  muscular  sys- 
tem and  circulatory  apparatus  and  brain.  But  in  the  developed 
organism  each  individual  cell  retains  only  the  faint  reminiscence 
of  each  type  of  function  except  the  one  for  which  it  has  been 
especially  developed ;  and  this  one  it  can  carry  out  in  exaggerated 
fashion.  The  particular  cells  that  have  made  themselves  mas- 
ters of  that  department  of  the  work  which  has  to  do  with  the 
ingestion  of  food  and  the  splitting  up  of  proteins  is  called  the 
digestive  apparatus ;  and  its  work  is  supplemented,  we  have  found 
reason  to  believe,  by  the  leucocytes  and  erythrocytes. 

But  when,  as  occasionally  happens  through  inadvertence,  a 
considerable  quantity  of  protein  in  the  unbroken  form  makes  its 
way  into  the  circulation  and  comes  thus  (unmodified)  in  contact 
with  the  body-cells  in  general,  it  is  as  useless  to  these  cells  as 
if  it  were  composed  of  utterly  unassimilable  materials. 

The  proof  of  this  is  that  proteins  thus  introduced  in  quantity 
are  excreted  unchanged  through  the  kidneys.  The  leucocytes  and 
erythrocytes,  to  be  sure,  deal  with  part  of  this  foreign  protein; 
but  their  capacity  is  limited,  and  beyond  that  nothing  remains  but 
to  eliminate  the  foreign  substance  as  rapidly  as  possible.  In 


MECHANISM   OF  PROTEIN   HYDROLYSIS  AND  IMMUNIZATION      77 

case  this  cannot  be  accomplished,  the  protein  which  might,  under 
other  conditions,  be  invaluable  as  food  for  the  tissues  becomes  a 
menace  through  a  mechanical  clogging  of  the  spaces  about  the 
cells,  and  perhaps  through  the  accumulation  of  partially  meta- 
morphosed product  as  the  result  of  the  activity  of  the  leucocyte. 
Antibodies  quite  different  from  antitoxins  will  be  developed  by 
the  leucocytes;  but,  of  course,  these  can  avail  only  if  the  foreign 
proteins  come  in  relatively  limited  quantity. 

Making  an  anticipatory  therapeutic  application,  it  is  clear  that 
the  ideal  to  be  aimed  at  when  proteins  are  introduced  hypodermi- 
cally  (as  in  Proteal  therapy),  is  to  give  the  dose  that  will  evoke 
a  maximum  corpuscular  response  with  a  minimum  introduction  of 
foreign  proteins  that  must  themselves  be  proteolyzed.  Whether 
this  may  best  be  accomplished  by  using  a  single  foreign  protein 
or  by  combining  a  number  of  such  proteins  is  an  important  prac- 
tical question  that  will  be  discussed  later  in  this  volume. 

So  much  by  way  of  recapitulation,  and  to  make  clear  the  dis- 
tinction that  I  conceive  to  exist  between  the  sources  and  the 
character  of  the  antibodies  as  evoked  by  antigens  that  on  one 
hand  are  protein  bodies  and  on  the  other  are  the  metamorphosed 
products  of  protoplasmic  activity — so-called  toxins. 

THE   COALITION   BETWEEN   RED   CORPUSCLES   AND  WHITE 

Reverting  now  to  the  latter,  in  continuance  of  the  theme,  it 
remains  only  to  point  out  that,  whereas  it  is  conceived  that  all 
the  cells  of  all  the  tissues  of  the  body  have  capacity  for  the 
production  of  antitoxins  in  response  to  small  moleculed  toxins, 
it  would  appear  that  there  is  one  type  of  cell  that  is  pre-eminently 
adapted,  by  virtue  of  its  location  in  the  organism,  to  absorb  these 
toxins  and  render  them  innocuous ;  at  the  same  time,  of  course, 
giving  out  the  residual  products  which  we  term  antitoxins.  The 
cells  in  question  are  the  red  corpuscles  of  the  blood. 

A  very  prominent  function  of  these  cells,  according  to  the  pres- 
ent thesis,  is  thus  to  shield  the  body-cells  in  general  against  the 
attacks  of  the  numerous  toxins  that  necessarily,  under  existing 
conditions,  find  their  way  more  or  less  continuously  into  the  blood 
stream.  In  particular,  to  shield  the  brain  cells,  because  they  take 
(in  Abderhalden's  experiments)  the  same  type  of  complex  nitro- 
gen compounds  that  have  affinity  for  the  cerebral  tissues.  Ordi- 
narily the  red  corpuscles  come  in  contact  with  them  first,  and 
thus  the  brain  is  protected. 

As  justification  for  the  conclusion,  we  have  the  entire  line  of 
analogical  reasoning  just  presented,  supported  specifically  by  the 
experiments  of  Abderhalden,  which  showed,  it  will  be  recalled, 
that  the  red  blood  corpuscles  manifested  exceptional  activity  in 


78      THE   PROTEOMORPHIC  THEORY   AND  THE   NEW    MEDICINE 

the  proteolysis  of  those  polypeptids  which  I  have  all  along  likened 
to  the  toxins. 

Of  course,  the  specific  antitoxins  developed  by  the  red  blood 
corpuscles  would,  in  the  nature  of  things,  be  liberated  into  the 
blood  plasma.  But  there  would  doubtless  be  a  good  many  com- 
pounds formed  that  could  not  advantageously  be  thus  disposed 
of;  and  possibly  it  is  to  meet  the  complications  thus  introduced 
that  the  body  has  developed  the  custom  of  destroying  vast  quan- 
tities of  the  red  blood  corpuscles  constantly  in  the  liver,  where 
the  refuse  matter  they  contain  may  be  promptly  eliminated  in  the 
form  of  bile.  It  may  be  doubted  whether  any  other  hypothesis 
hitherto  presented  more  plausibly  accounts  for  the  constant  de- 
struction of  red  blood  corpuscles  (estimated  to  represent  about 
three  per  cent,  of  the  entire  corpuscular  supply  daily),  which, 
at  first  blush,  seems  to  set  at  defiance  the  usual  bodily  custom 
of  conserving  materials. 

In  this  view,  then,  the  red  blood  corpuscles  have  an  immuniz- 
ing function  strictly  complementary  to  that  of  the  white  blood 
corpuscles,  and  no  less  important.  One  legion  of  cells  co-operates 
with  the  other,  each  having  its  own  special  field.  The  white 
corpuscle  deals  with  all  formed  bodies  and  full-sized  protein 
molecules  of  foreign  type  that  make  their  way  into  the  blood 
.stream.  The  red  blood  corpuscle  deals  with  the  later  cleavage 
products  of  protoplasmic  activity.  In  carrying  out  their  respec- 
tive tasks,  the  leucocyte  supplements  the  work  of  the  ferments 
of  the  digestive  tract;  the  red  corpuscle  supplements  the  work 
of  the  leucocyte  and  relieves  the  ultimate  tissues  in  considerable 
measure  of  the  task  of  protecting  themselves  against  small- 
moleculed  nitrogenous  end  products  that  might  prove  harmful. 

Interpreting  the  work  in  the  words  of  the  bacteriologist  and 
pathologist,  we  may  say  that  the  leucocyte,  in  the  pursuance  of 
its  general  scavengering  function,  produces  "complement"  that  is 
a  digestive  ferment  somewhat  of  the  order  of  trypsin;  and 
"antibodies"  of  the  types  known  as  bactericides,  bacteriolysins, 
opsonins,  and  precipitins;  also  antitoxins  to  neutralize  the  of- 
fensive or  defensive  toxins  put  forth  by  the  living  bacterium. 
Meantime  the  red  blood  corpuscles,  aided  and  supported  on  occa- 
sion by  various  and  sundry  of  the  specialized  tissues — liver,  kid- 
ney, muscle,  brain — produce  complements  of  a  different  order 
from  those  produced  by  the  leucocyte,  capable  of  dealing  only 
with  partially  hydrolyzed  protein  products ;  and  produce  also 
specific  antitoxins  that  chemically  neutralize  bacterial  toxins  and 
in  particular  the  final  by-products  of  bacterial  decompounding, 
but  do  not  attack  the  bacteria  themselves.  It  is  not  unlikely 
that  hemolysis  also  falls  within  the  scope  of  the  erythrocytic 
activities. 


MECHANISM   OF   PROTEIN    HYDROLYSIS  AND   IMMUNIZATION      79 

If  the  implications  of  the  theory  are  clearly  grasped,  it  will 
be  obvious  that,  according  to  the  present  view,  there  is  no  funda- 
mental distinction  between  the  various  "complements"  and  "anti- 
bodies" thus  defined.  The  word  "complement"  as  commonly 
used  merely  serves  to  define  such  members  of  an  endless  series 
of  ferments  as  are  relatively  susceptible  to  the  influence  of  high 
temperatures.  The  line  of  demarcation  thus  established  has  ob- 
vious practical  value ;  but  we  should  not  be  led  thereby  to  imag- 
ine a  duality  of  action  which  in  all  probability  does  not  exist  in 
fact. 

What  we  term  "complement"  in  any  given  case  is  the  ferment 
or  combination  of  ferments  regularly  developed  in  quantity  by 
the  cell  in  question  to  meet  the  more  or  less  habitual  needs  inci- 
dent to  the  ingestion  of  proteins  of  its  environment.  What  we 
term  an  "antibody"  in  any  given  case  is  one  of  a  series  of  fer- 
ments developed  in  response  to  a  specific  impulse  given  by  an 
individual  type  of  protein  or  protein  product.  The  trypsin  of 
the  leucocyte  would  stand  at  one  end  of  that  scale;  the  anti- 
toxins of  the  red  corpuscle  at  the  other;  but  there  would  be 
intermediate  forms  to  cover  all  the  field  between  the  two,  each 
enzyme  doubtless  overlapping  more  or  less  with  its  neighbors. 

That  the  general  ferments  or  complements  should  be  themola- 
bile  and  the  antibodies  relatively  thermostable  may  conceivably 
be  due  to  the  greater  complexity  of  the  former,  consistent  with 
their  more  generalized  function.  But  that  there  is  any  radical 
and  fundamental  distinction  in  "the  nature  of  the  two  types  of 
structures  seems  theoretically  improbable. 

The  demonstration  or  refutation  of  the  validity  of  this  assump- 
tion, however,  is  a  matter  for  the  chemistry  of  the  future,  with 
its  extended  knowledge  of  the  nature  of  enzymes  in  general. 


CHAPTER  II 
THE  PROTEOLYTIC  MECHANISM  IN  OPERATION. 

Such,  then,  is  the  immunizing  mechanism  of  the  body  as  I 
conceive  it:  (1)  a  system  of  lymphoid  tissues,  comprising  lym- 
phatics, bone  marrow,  and  spleen,  and  sending  into  the  field 
legions  of  leucocytes  and  still  greater  legions  of  red  corpuscles 
to  support  them;  (2)  body-cells  of  many  types  standing  in  the 
background,  each  equipped  only  for  individual  defense;  and  (3) 
the  liver  and  kidneys  as  the  chief  excretory  organs  of  the  by- 
products of  the  conflict.  This  is  the  system  which  guards  the 
body  from  within,  as  skin  and  mucous  membrane  guard  it  from 
without,  against  the  intrusion  of  foreign  proteins  of  every  type, 
and  against  the  products  of  proteid  activity. 

Some  further  details  as  to  manner  of  working  of  this  impor- 
tant mechanism  may  perhaps  be  presented  to  best  advantage  if  we 
make  inquiry  as  to  precisely  what  takes  place  on  the  various 
occasions  when  the  efficacy  of  the  defensive  mechanism  is  put 
to  an  exceptional  and  decisive  test. 

Let  us  assume  a  case  in  which  a  few  molecules  of  unbroken 
protoplasm  have  found  their  way  through  the  intestinal  wall — 
evading  the  pepsin  and  trypsin  and  erepsin  of  the  digestive  tract 
— and  enter  the  blood  stream.  This  is  not  a  strictly  normal  oc- 
currence, to  be  sure,  but  it  must  be  a  very  common  one,  under 
slightly  maladjusted  conditions  of  digestion,  as  the  experiments 
already  cited  show.  In  these  experiments  the  proteins  proved 
thus  to  enter  the  circulation  unbroken,  including  those  of  egg 
albumen,  blood  serum,  and  milk.  So  we  may  fairly  assume  that 
any  of  the  ordinary  food  proteins  may  on  rather  frequent  occa- 
sions find  their  way  in  small  quantities  into  the  blood  stream. 
We  have  now  to  inquire  what  happens  to  them  there. 

The  inquiry  has  practical  interest  for  the  clinicism  no  less  than 
for  the  physiologist,  because  it  is  obvious  that  it  applies  equally 
to  the  bodily  activities  responsive  to  the  therapeutic  introduc- 
tion of  a  foreign  protein,  through  the  hypodermic  injection  of  a 
serum  or  vaccine  or  proteal.  There  are  very  important  quanti- 
tative differences,  however,  evidenced  in  the  varying  degrees  of 
toxicity,  as  interpreted  by  the  clinicism. 

Let  us  first  consider  the  case  in  which  the  introducing  protein 

comes  through  the  intestinal  wall,  through  partial  failure  of  the 

normal  digestive  enzymes.     Then,  according  to  assumption,  the 

protein  is  a  mere  fragment  of  a  normal  food  stuff;  but  it  is  a 

80 


THE   PROTEOLYTIC    MECHANISM    IN   OPERATION  81 

disturbing  element  in  its  present  location.  According  to  the 
theory  here  presented,  what  happens  to  it  is  this :  the  leucocytes 
having  had  to  deal  with  this  particular  type  of  protoplasm  many 
times  before  have  already  secreted  into  the  blood  serum  an 
enzyme  (allied  to  trypsin)  that  is  capable  of  attacking  the  pro- 
tein and  accomplishing  the  early  stages  of  its  proteolysis.  This 
process  will  be  facilitated  if  the  molecules  of  foreign  protoplasm 
chances  to  be  engulfed  in  the  body  of  a  leucocyte.  But  in  any 
event  the  leucocytic  enzymes  will  hydrolyze  the  protein  to  the 
peptone  stage;  conceivably  to  the  stage  of  polypeptids. 

At  this  stage  the  partially  hydrolyzed  foreign  protein  is  turned 
over  to  the  red  blood  corpuscles.  To  them  these  particular 
polypeptids  are  familiar  materials,  since  they  have  dealt  with 
their  like  often  enough  before,  and  the  particular  department  of 
their  enzymes-making  apparatus  that  will  deal  with  these  specific 
polypeptids  is  in  good  working  order;  indeed,  the  enzymic  prod- 
ucts are  already  in  the  blood  stream.  So  the  further  hydrolysis  of 
the  intruding  matter  is  rapidly  carried  forward ;  with  the  result 
that  presently  the  main  bulk  of  the  material  has  been  transformed 
into  amino-acids — thus  supplying  normal  material  for  the  uses 
of  the  cells  that  are  to  build  up  the  specific  body  proteins. 

We  must  suppose,  however,  that  there  is  a  small  residual  mat- 
ter, of  doubtful  constitution,  which  has  not  been  thus  hydrolyzed ; 
for  the  complete  hydrolyzation  of  a  protein  through  the  agency 
of  enzymes  has  not  been  accomplished  in  the  laboratory,  and  we 
have  no  reason  to  suppose  that  it  is  accomplished  in  the  body. 
It  requires  from  two  to  five  hours  of  digestion  in  strong  hydro- 
chloric acid  to  hydrolyze  protein  completely  in  vitro;  the  organ- 
ism has  no  enzymes  of  corresponding  power. 

But,  according  to  hypothesis,  the  residual  molecules,  whatever 
their  exact  nature  (uric  acid,  urea,  bilurubin),  have  been  largely 
or  perhaps  exclusively  developed  in  the  bodies  of  the  red  cor- 
puscles ;  with  the  result  that  the  corpuscles  themselves  are  more 
or  less  damaged.  The  residual  molecules,  that  is  to  say,  are 
poisonous  to  protoplasm.  The  red  corpuscle  in  retaining  or  ab- 
sorbing them  is  thus  injuring  itself,  but  protecting  the  body-cells 
that  would  otherwise  absorb  the  poison. 

But  whereas  such  an  injury  to  the  body-cells  would  be  highly 
detrimental  to  the  entire  organism,  the  injury  to  the  red  blood 
corpuscle  is  not  necessarily  a  matter  oj  consequence.  The  cor- 
puscle bearing  its  poison  is  whirled  on  in  the  blood  stream  until 
it  comes  to  the  liver,  and  there  destroyed,  its  noxious  molecules 
being  discharged,  with  countless  others  of  similar  origin,  into 
the  bile  duct. 

It  would  be  interesting  to  inquire  as  to  just  what  is  the  char- 


82      THE   PROTEOMORPHIC   THEORY   AND  THE    NEW    MEDICINE 

acter  of  the  physiological  action  that  leads  to  the  destruction 
of  the  red  corpuscle,  but  this  would  carry  us  too  far  afield. 

Conceivably  osmotic  pressure  alone  may  suffice ;  the  substance 
of  the  hemoglobin  being  in  part  decompounded  by  the  imbibed 
foreign  enzymes,  and  its  osmotic  pressure  thus  enhanced.  Rup- 
ture would  then  be  likely  to  take  place  in  the  liver,  because  that 
organ  serves  as  a  great  lagoon  in  which  blood  from  the  portal 
vein  becomes  relatively  static,  and  reduced  in  pressure.  Some- 
what similar  conditions  in  this  regard  obtain,  it  may  be  added, 
in  the  spleen ;  and  it  is  perhaps  significant  that  many  physiologists 
believe  that  this  organ  also  is  the  seat  of  erythrocytolysis. 

In  any  event,  through  osmotic  or  chemical  action  disruption 
does  occur,  and  the  unassimilable  remnant  of  the  foreign  proteid 
is  thus  extruded  into  the  intestine,  whence  it  originally  came; 
the  general  protein  content  of  the  red  corpuscle  (transformed 
now  through  partial  disruption  into  globulin  and  albumin)  being 
liberated  to  contribute  to  the  regular  protein  contents  of  the  blood 
serum. 

It  requires  but  the  most  casual  study  of  corpuscles  in  the  Tois- 
son  solution  in  the  counting  chamber  to  suggest  the  widely  differ- 
ing conditions  of  osmotic  pressure  among  the  corpuscles  of  a 
drop  of  blood,  and  the  diversified  conditions  that  obtain  in  asso- 
ciation with  various  toxaemias.  In  freshly  drawn  supposedly 
normal  blood  all  the  erythrocytes  will  appear  smooth  in  contour, 
the  cell-membrane  seemingly  taut.  But  in  the  course  of  half 
an  hour  or  so  the  appearance  of  most  of  the  corpuscles  may  be 
utterly  changed.  They  become  shriveled,  and  assume  the  appear- 
ance of  diminutive  sea  urchins.  Modifications  of  size  and  con- 
tour continue,  presumably,  until  the  contents  of  the  cell  become 
isotonic  with  the  saline  medium. 

It  is  my  belief  that  valuable  inferences  may  be  drawn  as  to  the 
physiological  and  pathological  activities  of  the  corpuscles,  in 
individual  cases,  from  study  of  the  variable  time  and  character 
of  modification  undergone  by  the  corpuscles  in  thus  reaching  a 
state  of  osmotic  equilibrium. 

For  example,  cells  that  shrivel  in  a  medium  of  moderate  hyper- 
tonicity  may  be  assumed  to  have  a  large-moleculed  content.  And 
this  gives  presumptive  evidence  that  the  functions  of  completing 
hydrolysis  of  absorbed  peptones  or  polypeptids  is  being  per- 
formed sluggishly  or  inadequately.  In  such  a  case  compensation 
may  for  a  time  be  effected  by  increase  of  red  corpuscles,  and  we 
are  confronted  with  the  clinical  paradox  of  a  virtual  ansemia  in 
which  the  number  of  erythrocytes  is  perhaps  five  and  a  half  or  - 
six  million. 

If  in  such  a  case  the  white  corpuscles  appear  fairly  normal  in 
number,  quality,  and  differential  count,  it  may  be  inferred  that 


THE    PROTEOLYTIC    MECHANISM    IN    OPERATION  83 

the  patient  suffers  from  protein  end  product  absorption — a  com- 
mon and  characteristic  form  of  intestinal  toxaemia. 

In  a  typical  case  of  this  description  recently  under  my  obser- 
vation, the  patient  is  a  youth  of  eighteen,  with  no  pronounced 
clinical  symptoms  other  than  habitual  constipation  and  suscepti- 
bility to  infection  ("catches  cold"  readily;  has  occasional  crops 
of  boils).  Pulse  68;  blood  pressure,  120-80;  haemoglobin,  85-90. 
The  white  corpuscles  numbered  6,400,  and  on  the  smear  ap- 
peared normal  purple  and  showed  no  tendency  to  clump.  Red 
corpuscles,  5,608,000,  largely  checkered  and  vacuolated  when 
fresh  in  (diluted)  Toisson  solution;  platelets  fairly  numerous. 
After  three  hours  ninety  per  cent,  shriveled,  spiny,  more  or  less 
distorted  (a  condition  I  am  accustomed  to  refer  to  in  my  labora- 
tory notes  as  the  "sea  urchin"  effect)  ;  so  small  as  to  show  pro- 
nounced Brownian  movement. 

Closely  similar  blood  conditions  are  often  found  in  patients 
suffering  from  chronic  arthritis.  This  is  not  the  place,  how- 
ever, to  discuss  in  further  detail  the  pathological  and  clinical 
bearings  of  the  implied  disturbances  of  the  erythrocytic  func- 
tion of  ultimate  protein  hydrolysis.  That  observation  of  the 
corpuscles  in  this  connection  have  practical  bearing  on  problems 
of  disturbed  digestion  and  assimilation  clinically  spoken  of  as 
autointoxication  and  intestinal  toxaemia,  will  be  obvious.  Full 
discussion  of  the  phenomena  in  question,  with  particular  refer- 
ence to  acidosis  and  the  rheumatoid  condition,  will  be  given  in  a 
subsequent  chapter. 

THE  PHENOMENA  OF  ANAPHYLAXIS 

But  suppose  now  that  the  protein  that  enters  the  blood  stream, 
instead  of  being  the  product  of  a  familiar  foodstuff  is  a  protein 
of  an  unusual  type — that  is  to  say,  one  that  the  organism  does 
not  habitually  ingest.  Or  suppose  that  the  protein,  although  of 
a  familiar  type,  is  introduced  in  rather  large  quantities.  In  either 
case  complications  arise;  and  these  complications  are  precisely 
similar  in  character  in  the  two  cases,  being  due  in  each  case  to 
the  inadequacy  of  the  protective  equipment,  as  will  appear  in  a 
moment. 

Illustrative  cases  in  point  are  the  laboratory  experiments  in 
which  a  foreign  protein  is  injected  into  the  system  of  a  rabbit 
or  guinea  pig;  and,  in  case  of  a  human  subject,  those  instances 
in  which  proteids  are  ingested  in  great  quantity  and  fail  of  nor- 
mal complete  digestion. 

In  either  case  the  phenomena  may  result  that  have  become 
more  or  less  familiar  under  the  name  of  anaphylaxis.  It  is  a 
condition  of  toxicity  in  which  the  symptoms  clearly  indicate  in- 


84      THE    PROTEOMORPHIC   THEORY   AND   THE    NEW    MEDICINE 

volvement  of  the  brain — or,  at  all  events,  of  the  central  nervous 
system. 

In  the  laboratory  experiments  this  condition  of  so-called  ana- 
phylactic  shock  may  occur  after  a  single  inoculation  with  a  large 
dose  of  a  foreign  proteid ;  but  in  that  case  it  is  somewhat  delayed. 

The  condition  is  usually  induced  by  following  a  small  initial 
dose  of  protein  (which  has  no  apparent  effect)  with  a  larger 
one  at  an  interval  of  a  week  or  ten  days.  A  strictly  comparable 
condition  is  sometimes  produced  in  the  human  subject  through 
the  use  of  antitoxic  serums,  anaphylaxis  being  due  not  to  the 
antitoxin  itself,  but  to  the  foreign  blood  serums  (usually  that  of 
the  horse)  in  which  it  is  suspended.  In  the  case  of  the  animal 
in  the  laboratory,  the  condition  is  often  fatal,  sometimes  very 
rapidly  so.  In  the  case  of  the  human  subject,  it  may  constitute 
a  serious  "serum  disease." 

My  personal  observation  of  the  phenomena  of  anaphylaxis  in 
the  human  subject  has  been  chiefly  associated  with  the  thera- 
peutic administration  of  sheep  serum  (antithyroid)  and  various 
vegetable  proteins  (proteals).  A  mild  anaphy lactic  reaction  may 
manifest  itself  locally,  a  few  hours  after  the  hypodermic  injec- 
tion is  given,  by  a  condition  of  erythema  at  the  point  of  injec- 
tion, involving  only  a  small  locus,  or  in  some  cases  extending  to 
the  entire  arm.  There  may  be  marked  ecchymosis  of  the  tissues, 
with  attendant  swelling  lasting  for  twenty-four  or  forty-eight 
hours. 

Whether  or  not  there  is  pronounced  local  reaction,  there  may 
be  a  general  reaction  two  or  three  hours  after  the  protein  is 
injected,  manifested  by  rise  in  temperature,  accelerated  pulse, 
feeling  of  malaise,  and  a  more  or  less  pronounced  chill.  These 
symptoms  disappear  presently,  without  calling  for  treatment. 

Very  different  are  the  manifestations  of  acute  anaphylactic 
shock  that  may  occur  when  a  patient  who  for  some  time  has  been 
under  protein  treatment  receives  by  accident  a  full  dose  of  the 
protein  into  a  vein.  The  anaphylactic  reaction  supervenes  in  the 
course  of  fifteen  or  twenty  seconds.  The  patient's  face  flushes 
violently,  more  or  less  severe  pains  are  located  in  the  head  and 
back,  and  the  pronounced  dyspnoea  simulates  an  acute  attack 
of  asthma.  In  extreme  cases  the  patient  may  lose  conscious- 
ness. The  violent  symptoms  usually  subside  rather  quickly,  al- 
though the  backache  may  persist  for  fifteen  or  twenty  minutes. 
Aromatic  spirits  of  ammonia  may  be  administered,  and  the  back- 
ache may  be  controlled  by  a  few  whiffs  of  chloroform.  Caffeine 
may  be  given  to  stimulate  the  heart.  But  all  these  measures 
are  more  or  less  of  the  nature  of  placeboid  palliatives.  The  pa- 
tient rallies  quickly  even  without  treatment,  and,  except  perhaps 
for  the  persistence  of  a  frontal  headache,  soon  feels  as  well  as 


THE   PROTEOLYTIC    MECHANISM    IN   OPERATION  85 

ever.  The  experience,  nevertheless,  is  an  unpleasant  one  for 
both  patient  and  physician. 

But  fortunately  an  anaphylactic  shock  of  this  character  from 
the  administration  of  a  protein  in  therapeutic  doses  is  exceed- 
ingly rare.  I  have  personally  witnessed  it  only  a  few  times  in 
the  course  of  an  experience  covering  the  administration  of  thou- 
sands of  doses  of  proteins.  Moreover,  it  would  appear  that 
the  vegetable  proteins,  when  partially  hydrolyzed,  as  in  the  prep- 
arations of  the  Proteals  now  made  in  my  laboratory,  do  not 
produce  anaphylactic  reactions  of  this  character.  A  possible 
explanation  of  this  gratifying  modification  will  be  attempted  in 
another  connection.  For  the  moment  we  are  concerned  with 
the  general  theory  of  the  anaphylactic  response. 

The  current  interpretation  of  this  condition  is  that  the  first 
injection  of  the  foreign  protein  has  "sensitized"  the  tissues,  so 
that  when  the  second  injection  occurs  there  is  a  sudden  and  mor- 
bid reaction.  Vaughan  explains  the  condition  far  more  plaus- 
ibly as  not  due  to  an  increased  sensitiveness  of  the  tissues,  but 
to  the  presence  of  enzymes  of  the  antibody  order  induced  by 
the  first  inoculation.  He  suggests  that  this  ferment  is  put  forth 
in  sufficient  quantities  not  merely  to  neutralize  the  protein  that 
called  it  forth,  but  to  saturate  the  blood  more  or  less ;  so  that 
when  the  second  dose  of  protein  appears  its  molecules  are  imme- 
diately broken  up  in  such  a  way  that  the  poison  group  is  released 
and  enabled  to  act  upon  the  tissues  toxically. 

But  this  suggestion  involves  an  obvious  and  fundamental  diffi- 
culty ;  it  assumes  that  the  antibody  put  forth  in  response  to  a 
foreign  protein  will  become  a  menace  instead  of  protection — 
which  precisely  reverses  the  prevalent  and  seemingly  correct  in- 
terpretation of  the  character  of  antibodies. 

According  to  the  view  of  the  present  writer,  the  rationale  of 
anaphylaxis  is  something  quite  different  from  this.  In  my  view, 
there  is  no  question  of  "sensitizing"  the  tissues  to  a  foreign  pro- 
tein ;  inasmuch  as  they  are  inherently  sensitive  to  all  proteins, 
foreign  or  otherwise,  at  the  proper  stage  of  disintegration.  Nor 
can  I  conceive  that  the  system  has  developed  the  incongruous 
habit  of  putting  forth,  in  response  to  a  protein  invasion,  anti- 
bodies that  will  necessarily  menace  the  system  itself  in  the  event 
that  the  invasion  is  repeated.  Such  a  phenomenon  would  seem- 
ingly be  an  exact  contradiction  of  the  established  customs  of  the 
organism. 

Yet  how  are  we  to  explain  the  anomalous  fact  that  the  organ- 
ism was  seemingly  unaffected  by  the  first  dose,  and  yet  was 
severely  poisoned  by  the  second  one,  administered  after  an  inter- 
val of  several  days? 

In  my  original  exposition  of  the  subject,  I  suggested  that  the 


86      THE   PROTEOMORPHIC   THEORY   AND  THE    NEW    MEDICINE 

Proteomorphic  theory  supplies  a  clear  and  definite  answer,  con- 
ditioned on  the  activities  of  the  white  and  red  blood  corpuscles 
in  the  regular  processes  of  assimilation,  as  already  outlined.  It 
assumes  that  the  white  blood  corpuscle  began  the  proteolysis  of 
the  first  dose  of  foreign  protein,  and  that  the  red  blood  corpuscle 
completed  it,  quite  as  before ;  but  that  the  specific  enzymes  of 
the  red  corpuscle  adapted  for  dealing  with  that  particular  protein 
were  present  in  very  limited  quantities  in  the  blood,  and  suscep- 
tible of  being  reformed  but  slowly  by  the  corpuscle,  precisely  be- 
cause the  organism  was  little  subject  to  that  particular  invasion. 
Meantime,  however,  the  more  generalized  enzymes  of  the  leuco- 
cyte, known  to  be  largely  non-specific  in  action,  were  able  to 
begin  hydrolysis  of  the  second  dose  of  foreign  protein  when  it 
appeared,  reducing  it  to  the  polypeptid  stage  at  which  the  red 
corpuscle  should  take  it  in  hand.  But  these  corpuscles,  ex- 
hausted at  the  moment  of  the  specific  ferment  (from  dealing 
with  the  first  dose)  are,  for  the  time  being,  helpless.  They  will 
gradually  replace  the  lost  enzymes,  of  course;  but  as  yet  they 
have  not  had  time  to  do  so,  at  least  in  adequate  quantity,  so  the 
foreign  polypeptids  pass  on  to  the  tissues,  and  some  of  them  are 
seized  on  by  the  brain  cells  with  disastrous  results. 

The  difficulty  arises,  it  will  appear,  from  the  fact  that  the 
enzyme  of  the  white  corpuscle,  which  begins  hydrolysis,  is  able 
to  attack  a  great  variety  of  proteins;  whereas  the  enzymes  to 
complete  the  hydrolysis  of  the  'resulting  polypeptids  must  be 
made,  in  the  case  of  any  specific  protein,  in  a  particular  depart- 
ment of  the  red  corpuscles'  laboratory. 

To  meet  this  necessity,  the  red  corpuscle  has  developed  a  very 
elaborate  type  of  protein,  each  molecule  of  its  hemoglobin  being 
composed  of  several  thousand  atoms;  and  under  ordinary  cir- 
cumstances it  is  able  to  manage  all  the  diverse  materials  that 
are  turned  over  to  it  by  the  leucocyte. 

But  the  circumstances  under  which  anaphylaxis  occurs  are 
not  ordinary.  It  is  only  a  protein  of  unusual  type,  or  a  protein 
that  comes  in  large  quantities  repeatedly,  that  can  induce  the 
condition,  through  disarranging  the  harmonious  working  of  the 
proteolytic  apparatus;  except,  indeed,  that  a  single  large  dose  of 
a  foreign  protein  may,  under  exceptional  conditions,  be  retained 
in  the  system  for  a  considerable  period  (instead  of  being  excreted 
rather  promptly  through  the  kidneys  as  is  usual),  in  which  case, 
obviously,  there  may  be  opportunity  for  the  white  corpuscle  to 
begin  proteolysis  of  larger  quantities  than  the  red  corpuscles  can 
handle. 

In  the  case  of  the  human  subject,  as  just  suggested,  anaphylaxis 
may  be  due  to  the  faulty  digestion  of  the  ordinary  food  pro- 
teids,  under  conditions  that  lead  to  the  absorption  of  an  excep- 


THE   PROTEOLYTIC    MECHANISM    IN   OPERATION  87 

tional  quantity  of  unbroken  protein.  It  may  also  result  from 
the  ingestion  of  an  unusual  type  of  protein,  notably,  of  course 
of  a  type  difficult  of  digestion.  In  general,  we  might  expect 
that  anaphylaxis  from  food  proteids  would  result  with  a  fre- 
quency in  direct  ratio  to  the  rarity  with  which  different  proteids 
are  digested.  It  is  confirmatory  that  anaphylaxis  from  eating 
shell-fish,  lobster,  and  various  fishes  seems  to  be  somewhat  more 
usual  than  that  resulting  from  the  proteins  of  beef,  mutton,  or 
fowl.  A  severe  case  of  anaphylaxis  from  eating  flesh  of  the 
snapping-turtle  has  come  within  the  observation  of  the  writer. 
Yet  for  most  people  the  flesh  of  the  snapping-turtle  is  entirely 
wholesome — as  wel)  as  exceedingly  palatable. 

It  should  be  observed  that  there  are  doubtless  idiosyncrasies 
of  individual  organisms  with  regard  to  parenteral  proteolysis, 
just  as  there  are  with  regard  to  digestion ;  and  this  accords  with 
the  familiar  laboratory  observation  that  not  all  animals  of  a 
species  suffer  to  the  same  extent  from  anaphylaxis  under  the 
same  conditions. 

In  the  consultation  room,  also,  marked  differences  are  to  be 
observed  among  different  patients.  Some  patients  are  pecu- 
ilarly  sensitive  to  any  protein;  others  are  peculiarly  resistant 
to  all  proteins.  Yet  others  appear  to  be  sensitive  to  one  protein, 
but  resistant  to  another.  Such  idiosyncrasies  are,  of  course,  quite 
to  be  expected.  It  does  not  appear,  however,  that  inherent  sus- 
ceptibility to  a  particular  pr6tein  is  necessarily  associated  with 
susceptibility  to  severe  anaphylactic  shock  from  the .  sudden  in- 
troduction of  a  large  dose  of  protein  into  the  system  previously 
"sensitized."  Such  "sensitization,"  in  the  view  here  represented, 
consists  in  surcharging  the  blood  with  corpuscular  enzymes 
capable  of  affecting  rapid  proteolysis  of  the  proteins  in  question. 

The  anaphylactic  shock  is  probably  to  be  interpreted  as  a  vaso- 
motor  phenomenon.  The  almost  instantaneous  onset  leaves  it 
scarcely  open  to  question  that  the  primary  action  is  exercised 
upon  the  vaso-motor  and  cardiac  centers  in  the  brain. 

The  reason,  presumably,  why  shock  takes  place  when  the  pro- 
tein is  injected  directly  into  the  vein,  and  not  when  the  injec- 
tion is  merely  subcataneous  or  intramuscular,  is  that  in  the  for- 
mer case  a  relatively  large  amount  of  protein  is  brought  instantly 
in  contact  with  the  brain  centers ;  whereas  in  the  latter  case 
absorption  is  slow  and  there  is  ample  opportunity  for  the  red 
corpuscles  to  perform  their  regular  functions  of  shielding  the 
brain  cells  by  themselves  absorbing  the  partially  hydrolyzed  pro- 
tein molecules. 

The  observed  fact  that  the  therapeutic  administration  of  the 
proteoses  does  not  tend  to  produce  the  same  anaphylactic  shock 
that  is  produced  by  the  full-sized  molecule  of  the  same  type  (for 


88      THE    PROTEOMORPHIC   THEORY   AND   THE    NEW    MEDICINE 

example,  alfalfa  seed  protein)  is  difficult  of  explanation.  The 
thought  naturally  suggests  itself  that  the  anaphylactic  shock  may 
be  due  to  the  action  of  the  full-sized  protein  molecule  on  the 
brain  cells,  which  is  not  entirely  consistent  with  the  explanations 
of  anaphylaxis  above  suggested.  It  should  be  understood,  how- 
ever, that  this  explanation  is  at  best  only  tentative.  The  phe- 
nomena of  anaphylaxis  are  exceedingly  puzzling  and  by  no  means 
fully  understood.  I  wish  frankly  to  state  that  no  other  hypothe- 
sis in  connection  with  the  general  thesis  of  the  Proteomorphic 
theory  is  presented  with  greater  diffidence  or  should  be  held 
with  greater  reserve  than  that  connected  with  anaphylaxis.  The 
full  and  satisfactory  explanation  of  the  subject  awaits  a  much 
more  comprehensive  and  penetrating  knowledge  of  the  general 
relations  of  foreign  proteins  in  the  blood  stream  to  the  central 
nervous  system  than  is  at  present  available. 

Nevertheless,  it  appears  to  me  that,  in  view  of  what  we  have 
already  seen  of  the  relations  of  the  red  corpuscles  to  the  process 
of  ultimate  protein  hydrolysis,  the  further  investigation  of  the 
phenomena  of  anaphylaxis  should  be  conducted  always  with  the 
newly  discovered  functions  of  the  red  corpuscles  clearly  in  mind. 

As  corroborating  the  view  just  presented,  according  to  which 
protein-product  intoxication  is  due  to  the  incapacitating  of  the 
red  corpuscle;  and  at  the  same  time  in  corroboration  of  the 
general  view  that  the  red  corpuscle  is  the  agent  called  upon  to 
deal  with  the  toxic  products  of  protein  generation,  we  may  recall 
the  clinical  fact  that  when  a  tapeworm  dies  in  the  intestinal 
tract,  and  decomposes  there,  the  absorption  of  its  toxic  products 
may  induce  the  condition  known  as  bothriocephalus  anemia,  a 
characteristic  symptom  of  which  is  the  very  great  and  persistent 
reduction  in  the  numbers  of  the  red  blood  corpuscles. 

The  red  cells  absorb  the  toxin,  and  effect  its  removal  through 
the  liver ;  but,  owing  to  the  persistence  of  the  supply,  such  num- 
bers of  the  corpuscles  are  involved  that  their  ranks  are  presently 
depleted,  the  cytogenic  apparatus  being  unable  to  manufacture 
them  at  so  abnormal  a  rate.  The  general  symptoms  of  pernicious 
anemia,  due  to  reduction  of  the  oxygen-  and  food-carriers,  fol- 
low as  a  matter  of  course ;  but  all  the  symptoms  clear  up  rapidly 
so  soon  as  the  dead  worm  is  expelled  from  the  bowel. 

THE  SYNTHESIS  OF  PROTEIN 

Incidentally,  it  may  be  urged  that  the  profound  systemic  dis- 
turbances that  accompany  a  reduction  in  the  number  of  red  blood 
corpuscles  in  this  case  would  never  result  were  the  chief  func- 
tion of  these  cells  merely  to  carry  oxygen,  as  is  commonly  con- 
ceived. Under  ordinary  conditions  the  systemic  cells  require  but 


THE   PROTEOLYTIC    MECHANISM    IN   OPERATION  89 

a  fraction  of  the  oxygen  that  the  red  corpuscles  can  carry,  as 
proved  by  the  fact  that  protein  metabolism  is  unchanged  when 
the  corpuscles  are  artificially  reduced  in  number  by  thirty  per 
cent. 

The  new  physiological  studies  which  suggest  that  air  may  be 
breathed  over  and  over  without  detriment — that,  in  short,  the 
"fresh  air"  fetich  is  founded  on  a  misconception  of  the  needs  of 
the  organism — is  of  peculiar  interest  in  this  connection. 

In  any  event,  it  would  not  seem  to  have  been  necessary  to 
build  a  cell  of  an  intricate  type  of  protein  merely  to  carry  oxygen. 
Nor  is  it  clear  why  the  substance  of  the  red  corpuscle  should 
contain  nucleo-protein  were  it  merely  an  oxygen-carrier. 

But  there  was  need  of  a  cell  carrying  a  molecule  of  intricate 
structure,  in  which  might  be  stored  the  potentialities  of  an  in- 
finite number  of  atomic  recombinations  having  their  tangible  rep- 
resentation in  the  output  of  endless  series  of  enzymes  calculated 
to  carry  the  hydrolysis  of  proteins  to  its  ultimate  stages ;  as  also 
to  prove  antidotal  to  an  unending  series  of  toxic  by-products  of 
protein  metabolism  in  the  living  or  dead  tissues  of  the  number- 
less species  of  animals  and  plants  and  micro-organisms  with 
which  the  environment  teems. 

In  the  evolutionary  history  of  the  race,  these  needs  have  in- 
creased pari  passu  with  the  increasing  activities  of  the  individual 
organism,  and  the  correspondingly  varied  character  of  the  en- 
vironment contact.  And  so  we  find,  as  we  come  up  the  animal 
scale,  that  the  red  blood  corpuscles  constantly  increase  in  rela- 
tive number  in  the  blood  stream.  In  fishes  the  red  corpuscles 
form  about  twenty  per  cent,  of  the  total  volume  of  the  blood ; 
in  frogs  about  twenty-five  per  cent.;  with  mammals  it  rises  to 
from  forty  to  fifty  per  cent.,  and  the  proportion  of  red  cor- 
puscles to  leucocytes  rises  in  something  like  the  same  proportion. 

The  primitive  and  generalized  leucocyte  retains  from  first  to 
last  the  same  appearance  and,  as  I  believe,  fulfills  the  same  prim- 
itive functions.  It  is  a  wandering  phagocyte  in  the  vascular 
system  of  the  sponge ;  it  remains  a  wandering  phagocyte  in  the 
vascular  system  of  man. 

In  the  primordial  state  the  red  cell  was  relatively  large  and 
nucleated  as  it  still  is  in  the  embryonic  state,  and  in  certain 
reversional  diseased  conditions. 

But  in  the  developed  condition  the  reproduction  of  the  cor- 
puscles devolves  upon  the  mother  cells  in  the  red  bone  marrow 
so  the  corpuscle  itself  needs  no  nucleus — or  perhaps  we  should 
rather  say  that  it  is  all  nucleus,  since  it  contains  nucleic  acids. 
It  is  decreased  in  size,  giving  it  relative  increase  of  surface, 
that  it  may  more  effectively  patrol  its  environment ;  and  it  is  sent 
forth  from  the  mother  cells  in  such  galaxies  that,  under  normal 


90      THE   PROTEOMORPHIC   THEORY   AND  THE   NEW    MEDICINE 

conditions,  there  are  five  million  individuals  in  each  cubic  mil- 
limeter of  the  blood-plasm. 

In  some  of  the  lower  mammals  the  number  is  far  larger — in 
the  goat,  for  example,  upward  of  ten  million;  in  the  sheep,  up- 
ward of  fourteen  million.  Goat  and  sheep  are  not  inordinately 
active  creatures.  Their  oxygen  needs  can  scarcely  be  so  great 
as  those  of  birds,  which  are  said  to  have  only  from  one  million 
to  four  million  red  corpuscles  to  the  cubic  millimeter.  But  the 
herbivorous  animals  ingest  large  quantities  of  protein-bearing 
foods,  and  it  is  probable  that  the  proteolytic  demands  made  upon 
their  corpuscles  are  far  greater  than  in  case  of  animals  whose 
diet  includes  a  large  proportion  of  carbonaceous  and  fatty  foods. 

But,  regardless  of  relative  numbers,  the  red  corpuscles  lead 
a  precarious  life.  Millions  on  millions  of  these  cells  are  anni- 
hilated every  hour  in  the  juggernaut  of  the  liver.  It  has  been 
estimated  that  the  destruction  amounts  to  three  per  cent,  of  the 
total  number  each  day — say,  150,000  corpuscles  to  each  cubic  mil- 
limeter of  blood,  or  an  aggregate  bulk  of  perhaps  sixty  grams 
in  the  entire  body.  To  gain  a  clear  conception  of  what  this  means, 
recall  that,  according  to  Atwater's  estimate,  a  man  of  average 
size  requires  only  92  grams  of  protein  daily  to  maintain  the 
nitrogen  balance.  Chittenden  makes  the  amount  far  less.  Yet 
the  ranks  of  the  corpuscles  thus  perpetually  depleted  are  no  less 
perpetually  replenished.  To  build  the  new  cells  requires  a  con- 
stant supply  of  materials  capable  of  being  elaborated  into  an 
intricate  type  of  protein.  To  build  each  molecule  of  this  proto- 
plasm requires  some  thousands,  in  the  aggregate,  of  atoms  of 
carbon  and  hydrogen  and  oxygen  and  the  elusive  nitrogen ;  some 
hundreds  of  molecules  of  amino-acids,  the  materials  directly 
utilized. 

The  total  energy  required  in  the  building  up  of  these  intricate 
molecules  in  the  bodies  of  uncountable  myriads  of  red  corpuscles 
hour  after  hour  and  year  after  year,  throughout  the  life  of  the 
individual  organisms,  is  colossal.  Each  red  corpuscle  is  a  pro- 
teid  body,  its  substance  composed  in  part  of  hemoglobin,  the 
formula  for  which  has  been  computed  as  C758H1203N195O218S3. 
To  suppose  that  the  organism  exhausts  this  material  and  wastes 
the  energy  essential  to  its  compounding  merely  to  produce  a  trans- 
porter of  unmodified  oxygen  would  require  a  reversal  of  all  our 
conceptions  of  economy  of  management  in  the  cellular  body  poli- 
tic. Yet  such  is  the  current  conception  of  physiologists  in  general. 

But  there  has  been  experimental  evidence  at  hand  for  many 
years  that,  if  properly  interpreted,  would  dispel  this  miscon- 
ception. As  long  ago  as  1872  Bauer,  in  Voit's  laboratory,  stud- 
ied the  results  of  bloodletting  in  the  dog,  and  found  that  when 
from  eighteen  to  twenty-seven  per  cent,  of  the  total  blood  in  the 


THE   PROTEOLYTIC    MECHANISM    IN   OPERATION  91 

dog's  body  was  removed,  there  was  increased  proteid  metabolism, 
but  no  change  in  the  carbon  dioxide  elimination.  Some  years 
later  Finkler,  in  Pfliiger's  laboratory,  withdrew  one-third  of  the 
total  blood  from  a  dog,  thereby  reducing  the  rapidity  of  blood- 
flow  in  the  femoral  artery  by  one-half,  without  producing  any 
change  in  the  quantity  of  oxygen  absorbed  or  of  carbon  dioxide 
exhaled.  More  recently  Hawk  and  Gies  have  confirmed  the 
early  experiments  to  the  extent  of  showing  that  there  is  a  higher 
proteid  metabolism  after  bloodletting. 

Such  experiments  are  utterly  disconcerting  so  long  as  we  con- 
sider the  red  blood  corpuscle  only  as  a  carrier  of  oxygen.  Note 
the  conditions :  the  blood  is  reduced  in  quantity  even  by  a  third, 
the  corpuscles  being,  of  course,  reduced  proportionately.  Yet 
the  absorption  of  oxygen  and  the  giving  out  of  carbon  dioxide 
are  unmodified ;  and,  even  more  strange  to  relate — according  to 
accepted  physiological  teaching — the  rate  of  proteid  metabolism 
is  increased. 

There  is  nothing  in  the  least  anomalous  about  these  phenomena, 
however,  if  interpreted  in  the  light  of  the  Proteomorphic  theory. 
In  this  view,  the  mother  cells  that  produce  the  red  corpuscles, 
together  with  those  that  produce  the  leucocytes,  constitute  the 
great  protein-synthesizing  mechanism  of  the  body.  Out  of  the 
amino-acids  in  the  blood  stream  and  lymph  stream,  according 
to  my  belief,  the  mother  cells  of  bone  marrow  and  spleen  and 
lymph  nodes  build  up  protein  of  the  specific  types  characteristic 
of  the  particular  organism,  storing  it  hour  by  hour  in  the  bodies 
of  unending  series  of  offspring  which  we  call  leucocytes  and  red 
blood  corpuscles.  The  protein  of  their  bodies  will  be  ultimately 
discharged  into  the  blood  stream,  to  make  up  the  proteins  (globu- 
lin and  albumin)  of  the  serum,  the  great  common  food  supply 
for  all  the  tissues,  and  an  important  source  of  energy  for  the 
bodily  activities. 

What,  then,  could  be  more  natural  than  that  when  there  is 
5uch  depletion  of  the  ranks  of  the  corpuscles  through  hemor- 
rhage, the  cytogenic  mechanism  should  take  on  exceptional  activ- 
ity, in  the  effort  to  make  amends  for  the  loss?  But,  of  course, 
the  bodies  of  the  corpuscles,  being  themselves  proteins,  cannot  be 
built  up  without  requisitioning  a  supply  of  protein-building  mate- 
rial and  giving  out  a  certain  amount  of  left-over  material  as 
nitrogenous  waste. 

Hence  the  observed  increase  in  the  protein  metabolism,  after 
severe  hemorrhage — which  might,  in  the  light  of  this  theory, 
have  been  predicted  in  advance  of  the  experiment.  As  to  the 
lack  of  increase  in  oxygen  intake  and  carbon  dioxide  outgo,  that 
only  furnishes  another  piece  of  incidental  evidence  that  no  such 
number  of  red  blood  corpuscles  is  necessary  as  that  normally 


92      THE    PROTEOMORPHIC    THEORY   AND   THE    NEW    MEDICINE 

found  in  the  body  merely  to  carry  on  the  work  of  oxygen  con- 
veying. The  necessity  for  an  unfailing  oxygen  supply  is  so 
great  that  provision  is  made  for  a  supply  far  in  excess  of  the 
average  needs  of  the  organism,  as  the  bloodletting  experiments 
show. 

Without  minimizing  the  value  of  the  services  of  the  red  blood 
corpuscles  as  a  carrier  of  oxygen,  then,  we  may  safely  assume 
that  its  service  as  a  provider  of  body  protein  is  at  least  as  great. 
A  realizing  sense  of  the  significance  of  this  function  comes  to  us 
when  we  reflect  that  the  intricate  bodies  of  the  red  corpuscles  are 
built  up  in  such  numbers,  that,  massed  together,  they  make  up  a 
bulk  of  about  four  pounds  in  the  body  of  a  man  weighing  one 
hundred  and  sixty  pounds. 

So  this  erythrocytic  body  surpasses  in  size  every  other  organ 
in  the  body  with  the  single  exception  of  its  collaborating  organ, 
the  liver.  The  fact  that  the  individual  cells  of  this  great  organ 
are  scattered  should  not  have  blinded  physiologists  to  the  neces- 
sity for  the  assumption  that  so  massive  a  structure  must  have 
vastly  important  functions  in  addition  to  the  simple  task  of  car- 
rying oxygen.  In  point  of  fact,  if  the  analysis  just  presented 
be  accepted,  it  is  clear  that  this  anomalous  viscus  is  an  organ 
of  the  assimilative  system  having  a  share  in  protein  metabolism 
subordinate  to  no  other.  The  function  of  dealing  with  bacterial 
poisons  may,  after  all,  in  the  widest  view,  be  considered — even 
as  the  function  of  carrying  oxygen  must  be  considered — but  an 
incident  in  the  career  of  the  red  blood  corpuscle. 

Its  supreme  functions  are  to  supply  fuel  in  the  form  of  pro- 
tein for  the  bodily  activities,  and  to  complete  the  proteolysis  of 
foreign  and  native  proteins  in  the  blood  stream. 

Yet  the  incidental  function  of  aiding  the  leucocyte  to  deal 
with  bacterial  toxins  cannot  be  considered  an  insignificant  one, 
inasmuch  as  the  safety  of  the  organism  as  a  whole  may  at  any 
time  depend  upon  it.  Measured  in  terms  of  the  health  of  the 
human  individual,  and  even  in  human  life,  this  function  of  the 
red  corpuscle  has  paramount  importance.  It  would  be  rash  to 
assert  that  its  defensive  and  immunizing  functions  are  less  con- 
stantly called  into  action  or  less  important  in  their  results  than 
the  allied  functions  of  the  leucocyte.  Both  are  essential  to  the 
life  of  the  organism. 

I  have  suggested,  indeed,  that  the  immunizing  functions  of 
the  two  types  of  corpuscles  must  be  regarded  as  complementary, 
rather  than  as  in  any  sense  competitive.  It  has  been  suggested 
also  that,  to  a  certain  extent,  the  functions  overlap,  so  that  an 
enzyme  secreted  by  one  might  facilitate  the  work  of  the  other. 
It  was  tentatively  suggested  that  perhaps  opsonin,  which  so  con- 
spicuously aids  the  leucocyte  in  its  phagocytic  functions,  may  be 


THE   PROTEOLYTIC    MECHANISM    IN   OPERATION  93 

produced,  partly  at  least,  by  the  red  corpuscles  in  response  to 
bacterial  toxins.  But  in  general  it  is  probably  the  leucocyte, 
with  its  less  specialized  organization,  that  aids  the  red  corpuscles, 
rather  than  the  converse. 

As  a  typical  instance,  we  may  note  that  whenever  the  red 
corpuscles  are  decreased  in  number — say  from  vigorous  blood- 
letting— the  army  of  leucocytes  at  once  receives  notable  acces- 
sions, being  fully  replenished  within  a  few  hours.  A  far  longer 
time  will  be  required  to  replace  the  vast  coteries  of  red  cor- 
puscles; meanwhile  it  is  the  part  of  wisdom  to  strengthen  the 
leucocytic  outposts.  In  some  cases  the  numbers  of  leucocytes 
may  become  so  great  that  their  bodies  must  have  a  really  sig- 
nificant share  in  replenishing  the  proteins  of  the  blood  stream, 
thus  making  partial  amends  in  this  direction  also  for  the  paucity 
of  red  corpuscles. 

THE  LEUCOCYTIC  BALANCE 

The  consideration  of  such  fluctuations  in  the  ranks  of  the  cor- 
puscles naturally  raises  a  question  as  to  how  the  leucocytic  bal- 
ance is  maintained. 

We  know  that  under  average  conditions  of  normal  health  the 
number  of  leucocytes  in  the  blood  stream  averages  about  six 
thousand  to  the  cubic  millimeter,  rising  to  about  eight  thousand 
three  or  four  hours  after  a  hearty  meal ;  and  that  the  number 
of  red  corpuscles  averages  about  five  million  to  the  cubic  mil- 
limeter and  is  less  subject  to  wide  variations  in  times  of  health. 

These  facts  are  so  familiar  that  we  scarcely  think  of  them 
as  requiring  explanation.  Yet  a  moment's  consideration  makes 
it  clear  that  the  maintenance  of  the  corpuscular  balance  is  a 
very  puzzling  phenomenon. 

How  are  the  mother  cells  in  the  bone  marrow  and  spleen,  for 
example,  to  know  that  protein  foods  have  been  taken  into  the 
stomach,  and  that  therefore  an  additional  supply  of  leucocytes  is 
needed?  How  are  these  mother  cells  to  know  that  there  has 
been  a  great  destruction  of  red  corpuscles  in  the  liver;  or  that 
a  wound  in  some  remote  part  of  the  body  has  resulted  in  a 
severe  hemorrhage?  How  are  they  to  know  that  a  colony  of 
pneumococci  has  found  lodgment  in  the  lungs,  and  that  fresh 
bands  of  phagocytes  are  required  to  fight  them?  How  are  they 
even  to  know  that  the  body  is  undergoing  vigorous  muscular  exer- 
cise; or  that  a  cold  bath  has  been  applied  to  the  skin? 

These  surely  are  interesting  questions.  Under  all  the  condi- 
tions just  noted,  the  cytogenic  cells  do,  in  point  of  fact,  take  on 
exceptional  activity,  and  produce  leucocytes  in  particular  in  un- 
wonted numbers. 


94      THE    PROTEOMORPHIC   THEORY   AND   THE    NEW    MEDICINE 

But  where  is  the  census-taker  of  blood  corpuscles  who  has  sig- 
naled to  them  that  these  exceptional  recruits  are  needed? 

The  more  one  considers  that  problem  the  more  puzzling  it 
seems ;  particularly  in  view  of  the  fact  that  the  bone  marrow  is 
but  doubtfully  connected  with  the  nervous  mechanism.  There 
are  sympathetic  nerves  in  connection  with  the  blood-vessels,  to 
be  sure,  and  these  might  serve  to  modify  the  blood  supply;  but 
we  can  scarcely  suppose  that  this  by  itself  can  control  the  activ- 
ities of  the  cytogenic  cells,  particularly  if  we  recall  that  the  blood- 
pressure  may  be  increased  indefinitely  without  necessarily  caus- 
ing leucocytosis ;  whereas,  on  the  other  hand,  active  generation 
of  leucocytes  may  occur  after  a  hemorrhage  that  has  reduced 
blood-pressure  to  the  minimum. 

It  does  not  necessarily  follow  from  this  that  the  sympathetic 
nervous  system  may  not  have  a  share  in  determining  the  activ- 
ities of  the  cytogenic  cells.  The  nervous  mechanism  may  well 
be  supposed  to  take  part  in  the  co-ordinating  of  the  activities 
of  the  various  mother  cells,  located  in  bone  marrow  and  spleen 
and  widely  scattered  lymph  nodes.  But  there  is  another  and 
quite  different  stimulating  and  co-ordinating  mechanism  which 
recent  studies  have  brought  into  the  foreground,  namely  the 
endocrinous  system,  with  its  various  internal  secretions  and 
hormones. 

The  messengers  of  this  system  travel  in  the  blood  stream  itself, 
as  also  doubtless  in  the  lymph  stream,  and  there  is  a  good  deal 
of  evidence  pointing  to  these  agents  as  the  stimulators  and  reg- 
ulators of  cytogenic  activity. 

I  have  had  verbal  report  from  a  colleague  of  cases  of  dia- 
betes and  Graves'  disease,  in  which  the  therapeutic  exhibition 
of  the  duodenal  hormone,  secretin,  is  reported  to  have  led  to  a 
rapid  and  extraordinary  rise  in  the  blood  count,  including  both 
leucocytes  and  erythrocytes.  It  is  interesting  to  note,  as  strongly 
supporting  the  Proteomorphic  theory,  that  this  corpuscular  in- 
crease is  said  to  have  coincided  with  very  marked  amelioration 
or  total  disappearance  of  the  symptoms  of  protein  poisoning 
that  characterize  the  disease.  But  at  the  moment  our  attention 
is  directed  to  the  probably  direct  connection  between  the  exhi- 
bition of  secretin  and  the  increased  activities  of  the  cytogenic 
cells. 

It  has  been  clearly  demonstrated  that  secretin,  as  produced  in 
the  duodenum,  enters  the  blood,  and  being  carried  to  the  pan- 
creas, stimulates  that  organ  to  the  production  of  its  charac- 
teristic tryptic  enzymes.  What  more  natural  than  that  the  same 
hormone  should  carry  similar  messages  to  the  bone  marrow  to 
stimulate  the  production  of  the  leucocytes  that  are  known  to 
secrete  an  enzyme  closely  allied  to  trypsin,  and  to  subserve, 


THE    PROTEOLYTIC    MECHANISM    IN    OPERATION  95 

within  the  vascular  mechanism,  a  function  of  proteid  digestion 
comparable  in  a  small  way  to  that  of  the  pancreas  itself? 

In  the  activities  of  the  hormone  secretin,  then,  if  these  infer- 
ences are  justified  we  find  a  solution  of  one  aspect  of  the  prob- 
lem of  maintenance  of  the  corpuscular  balance.  This  duodenal 
hormone  being  available  as  a  messenger,  the  fact  that  the  tissues 
of  the  bone  marrow  take  on  fresh  activities  in  response  to  the 
taking  of  food  into  the  stomach  seems  no  longer  mysterious, 
or  at  least  no  more  mysterious  than,  for  example,  the  increase 
in  the  activities  of  the  pancreas  brought  about  through  the  same 
agency. 

There  are  other  conditions,  however,  in  which  there  is  increase 
in  the  blood  count,  where  the  agents  through  which  the  cytogenic 
mechanisms  are  stimulated  may  not  be  so  readily  traced.  How, 
for  example,  shall  we  explain  the  leucocytosis  that  takes  place 
in  the  course  of  violent  muscular  exercise? 

Here  the  explanation  offered  must  be  regarded  as  altogether 
theoretical  and  provisional,  although  assuredly  not  lacking  in 
plausibility.  The  suggestion  I  would  make  is  that  the  increase 
of  leucocytes  here  is  due,  in  part  at  least,  to  the  increased  flow 
of  lymph  resulting  from  muscular  contraction.  It  is  known  that 
lymph  scarcely  flows  at  all  in  the  lymphatics  of  the  limbs  during 
quiescence,  but  is  stimulated  by  active  or  even  by  passive  move- 
ment. It  is  known  also  that  lymph  flowing  through  a  lymphatic 
gland  is  observed  to  emerge  with  an  increased  increment  of 
leucocytes,  and  the  inference  seems  unavoidable  that  the  leuco- 
cytes in  question  were  developed  in  the  lymph  node.  It  is  a  fair 
inference  that  their  rate  of  development  depends  on  the  rate 
of  flow  of  the  lymph  which  must  bring  the  food  albumen  to 
their  mother  cells,  and  if  this  be  admitted  the  increase  in  such 
of  the  leucocytes  as  are  developed  in  the  lymphatic  system  as 
a  result  of  muscular  exercise  is  accounted  for. 

The  function  of  the  lymphocytes  thus  brought  forth  would  be, 
perhaps,  to  assist  in  the  catabolism  of  products  of  protein  de- 
compounding associated  with  muscular  activities  (e.g.,  creati- 
nine)  or  of  materials  (proteins  or  fats)  for  supplying  foods 
or  fuels  to  these  cells.  In  the  original  presentation  of  the  Pro- 
teomorphic  theory  it  was  suggested  that  this  lymphocyte  assists 
in  the  decompounding  of  the  normal  serum  proteins.  I  am  now 
disposed  to  question  the  validity  of  this  assumption,  but  there 
were  certain  collateral  suggestions  that  perhaps  warrant  repro- 
duction of  the  paragraphs  in  question  here : 

"A  word  should  be  said  about  the  precise  service  which  the 
lymphocytes  thus  called  forth  in  response  to  muscular  action 
render  to  the  muscles  that  have  indirectly  engendered  them.  This 
lymphocyte  is  not  a  phagocyte,  but  it  may  have  to  do  with  the 


96      THE   PROTEOMORPHIC  THEORY  AND  THE   NEW    MEDICINE 

decompounding  of  the  normal  proteins  of  the  blood  serum 
(globulins  and  albumins).  These  are  decompounding  to  make 
fuel  (including  a  large  proportion  of  glycogen)  to  supply  energy 
to  the  body-cells,  and  notably  (1)  to  the  digestive  apparatus,  or 
(2)  to  those  most  important  dispensers  of  energy,  the  muscle 
cells. 

*"I  have  suggested  that  the  activity  of  the  muscle  cell  is  con- 
ditioned on  an  increase  of  osmotic  pressure  due  to  a  decom- 
pounding of  the  protein  within  the  cell.  This  is  necessarily 
accompanied  by  loss  of  energy,  expended  as  mechanical  energy 
and  as  heat.  The  physical  contents  of  the  cell  are  for  the  most 
part  not  wasted,  but  they  cannot  be  recompounded  into  proteins 
except  through  the  agency  of  energy  supplied  from  without. 
The  molecules  of  serum  protein,  suspended  in  blood  stream  and 
tissue  fluids,  are  decompounded  to  supply  this  energy.  And, 
according  to  the  present  view,  the  lymphocyte  is  the  agent  (or  at 
least  one  of  the  agents)  supplying  the  enzymes  that  inaugurate 
this  process  of  decompounding. 

"Hence  the  urgent  necessity  for  an  increased  supply  of  these 
leucocytes  in  times  when  the  muscles  are  called  upon  to  undergo 
excessive  contraction  for  prolonged  periods. 

"Hence,  also,  the  necessity  for  an  increase  of  lymphocytes 
after  the  ingestion  of  food,  to  aid  in  the  decompounding  of  serum 
proteins  to  supply  fuel  for  the  activities  of  the  glands  of  stom- 
ach and  pancreas  and  upper  intestines.  It  is  to  meet  this  need 
that  the  lymphocytes  are  observed  (as  we  have  seen)  to  be  sent 
out  in  greatly  increased  numbers  during  digestion.  The  supply 
of  digestive  ferments  cannot  be  made  out  of  nothing.  The  cells 
of  the  digestive  apparatus  cannot  keep  up  their  activities  un- 
less they  are  supplied  with  energy  from  without.  It  is  the 
province  of  the  serum  proteins  to  supply  this  energy,  in  part 
at  least,  here  as  in  the  case  of  the  muscles  and  other  tissues ; 
and  the  lymphocytes,  according  to  the  present  view,  have  a 
share  in  bringing  about  the  decompounding  of  the  serum  pro- 
teins, through  which  their  energy  is  liberated  and  made  available. 

"Should  the  numbers  of  the  lymphocytes  seem  inadequate  for 
such  a  task,  it  may  be  pointed  out  that  their  work  is  the  rela- 
tively simple  one  of  tearing  to  pieces  an  unstable  molecule.  Pos- 
sibly nothing  more  is  required  than  to  seize  on  a  single  group 
containing  the  protein  molecule's  three  sulphur  atoms  to  send 
the  entire  structure,  with  its  thousands  of  carbon  hydrogen,  oxy- 
gen, and  nitrogen  atoms,  tumbling. 

"Incidentally,  attention  may  be  called  to  the  curious  interest 
that  attaches  to  the  observation  of  the  cyclic  co-ordination  of 
parts  evident  in  the  observed  fact  that  the  lymphocytes  which 
(in  this  view)  aid  indirectly  in  the  production  of  the  digestive 


THE   PROTEOLYTIC    MECHANISM    IN   OPERATION  97 

ferments,  are  themselves  called  into  being  through  a  stimulus 
to  their  mother  cells  sent  out  as  a  hormone  messenger  from  the 
digestive  apparatus  itself. 

"Similar  cycles  of  co-ordination,  however,  are  not  unusual 
in  the  organism.  Indeed,  the  case  just  cited  of  the  lymphocytes 
developed  in  the  lymph  nodes  through  the  action  of  the  muscles, 
and  in  turn  serving  presently  to  aid  the  muscles  that  indirectly 
engendered  them,  furnishes  us  another  and  no  less  striking  illus- 
tration of  such  an  harmonious  dual  alliance," 

HORMONES  AND  THE  CORPUSCLE-BALANCE 

I  shall  not  here  discuss  in  detail  the  rationale  of  operation  of 
the  remaining  causes  that  are  observed  to  promote  leucocytosis. 
which  include  cold  baths  on  one  hand  and  fevers  of  microbic 
origin  on  the  other ;  contenting  myself  with  the  suggestion  that 
the  cold  bath  stimulates  the  vasomotor  apparatus  of  the  sympa- 
thetic system ;  and  that  the  bacterial  toxins,  when  present  in  the 
body  fluids,  doubtless  stimulate  the  cytogenic  apparatus  directly, 
while  the  bodies  of  the  bacteria  serve  as  a  food  pabulum  for 
the  leucocytes  that  may  lead  to  the  proliferation  of  the  latter 
through  cell  division. 

The  normal  leucocytosis  of  pregnancy  may  also  be  dismissed 
with  the  remark  that  it  furnishes,  in  view  of  the  known  inva- 
sion of  the  blood  by  foreign  (placental)  protein,  strong  cor- 
roborative evidence  for  one  phase  of  the  Proteomorphic  theory. 

It  seems  desirable,  however,  to  speak  a  little  more  in  detail 
(though  still  very  briefly)  of  the  part  in  maintaining  the  cor- 
puscular balance,  and  in  determining  the  activities  of  the  leuco- 
cytes, that  appears  to  be  played  by  the  endocrinous  organs;  in 
particular  by  the  adrenal  bodies,  the  thyroid  apparatus,  and  the 
glands  of  the  duodenum. 

To  establish  a  strong  a  priori  probability  that  some  at  least 
of  the  internal  secretions  directly  stimulate  the  activities  of  the 
corpuscles,  it  is  only  necessary  to  appreciate  the  fact  that  the 
corpuscles  themselves  must  be  classed  among  the  important  mem- 
bers of  the  endocrinous  system ;  and  to  recall  that  the  products 
of  the  various  ductless  glands  are  observed  to  interact  in  mutual 
stimulation  and  inhibition  of  the  organs  that  produce  them. 

When,  therefore,  to  cite  a  specific  instance,  it  is  observed  (as 
in  Cannon's  experiments)  that  a  sudden  increase  in  the  adrenal 
secretions,  induced  by  an  emotional  state  of  fear  or  anger,  results 
in  an  immediate  increase  of  glycogen  in  the  blood,  in  prepara- 
tion for  active  muscular  exertion,  we  may  justifiably  infer  that 
the  increase  has  been  brought  about,  in  part  at  least,  by  stimulus 
to  the  enzyme  forming  functions  of  the  lymphocyte,  induced  by 


98      THE   PROTEOMORPHIC  THEORY   AND  THE    NEW    MEDICINE 

the  presence  of  unusual  quantities  of  adrenalin  in  the  medium 
in  which  the  lymphocyte  is  suspended. 

Again,  the  observed  fact  that  persons  suffering  from  hypo- 
thyroidism  are  unduly  susceptible  to  the  attacks  of  bacterial  dis- 
eases, finds  suggestive  explanation  in  the  theory  that  a  normal 
supply  of  thyroidin  is  essential  to  the  normal  functioning  of  the 
cytogenic  apparatus.  Moreover,  there  is  a  certain  amount  of 
direct  evidence  for  the  claim  that  the  exhibition  of  thyroid 
extract  promotes  cytogenesis. 

An  increase  of  proteid  metabolism  has  been  observed  in  cases 
of  exophthalmic  goiter;  and  the  experiments  of  Anderson  and 
Bergman  show  a  similar  increase  from  the  giving  of  large  doses 
of  thyroid  extract.  If  the  role  of  the  corpuscles  in  proteolysis 
here  presented  be  accepted  as  valid,  these  observations  would 
form  another  bit  of  presumptive  evidence  linking  the  thyroid 
apparatus  with  the  cytogenic  mechanism. 

GENERAL  THERAPEUTIC  APPLICATIONS  OF  THE  PROTEOMORPHIC 
THEORY 

To  the  clinician  it  perhaps  does  not  so  greatly  matter  as  to 
what  theoretical  explanations  are  given  of  the  relations  of  hor- 
mones or  other  agent  to  the  stimulation  of  the  cytogenic  sys- 
tem. It  suffices  to  know  that  there  are  certain  available  agencies 
through  which  the  production  of  corpuscles  may  be  stimulated ; 
and  through  which,  therefore,  according  to  the  present  theory, 
the  processes  of  normal  protein  metabolism  and  incidentally,  but 
most  importantly,  the  immunization  of  the  patient  against  bac- 
terial diseases,  and  the  cure  of  these  diseases  themselves,  may 
be  facilitated.  What  these  agencies  are  has  been  suggested  in 
the  course  of  the  preceding  discussion. 

It  remains  now  to  make  a  few  practical  suggestions  as  to  the 
utilization  of  these  agencies ;  and,  in  general,  as  to  the  benefits 
that  may  accrue  to  the  patient  through  recognition,  on  the  part 
of  the  physician,  of  the  principle  that  the  blood  corpuscles,  white 
and  red,  are  the  all-important  agents  in  the  fight  against  bac- 
terial diseases. 

Let  us  take  as  a  typical  illustration — because  the  most  com- 
mon and  familiar — the  case  of  a  patient  suffering  from  tubercu- 
losis. 

The  tubercle  germ  invades  practically  every  human  organism. 
But  so  well  defended  is  the  average  system  against  its  attacks 
that  ninety  per  cent,  of  all  the  individuals  of  a  given  genera- 
tion are  able  to  throw  off  the  invader,  and  attain  full  individual 
immunity  to  its  attacks.  Such  immunity,  conditioned  on  the 


THE   PROTEOLYTIC    MECHANISM    IN   OPERATION  99 

hereditary  status  of  the  germ-plasm,  is  passed  on  to  the  offspring 
of  the  individual. 

But  ten  per  cent,  of  the  individuals  of  each  generation  are  not 
able  thus  to  ward  off  the  attacks ;  on  the  contrary,  they  suc- 
cumb to  it,  and  after  all  their  tissues  are  devitalized  to  an  extraor- 
dinary degree,  they  ultimately  die.  Their  failure  to  fight  off  the 
germs  is,  of  course,  due  to  an  inherent  lack  in  the  make-up  of 
their  defensive  mechanism.  The  mechanism  in  their  leucocytic 
and  erythrocytic  apparatus  that  should  produce  anti-ferments 
against  the  tubercle  germ  is  either  altogether  absent  or  is  de- 
vitalized and  minimized  in  efficiency.  The  result  is  that  their 
tissues  are  in  a  condition  comparable  to  that  which  the  student 
of  anaphylaxis  speaks  of  as  "sensitization,"  and  which  I  have 
suggested,  should  be  considered  merely  as  lack  of  defence.  Re- 
gardless of  the  precise  terms  of  the  explanation,  they  are  sus- 
ceptible to  the  attacks  of  the  germs,  and  this  inherent  sus- 
ceptibility may  be  passed  on  to  their  offspring. 

It  is  of  important,  even  if  of  incidental,  interest  to  recall  that, 
according  to  the  recent  studies  of  heredity,  this  susceptibility 
appears  to  act  as  a  Mendelian  recessive. 

That  is  to  say,  a  susceptible  person,  mated  with  a  normal  or 
resistant  person,  will  have  offspring  that  are  normally  resistant, 
but  who  contain  in  their  germ-plasm,  as  a  recessive  tract,  the 
factors  of  susceptibility  or  lack  of  immunity.  If  such  personally 
resistant,  but  potentially  susceptible,  individuals  are  mated,  one 
of  their  offspring  in  four,  on  the  average,  will  be  susceptible. 
This  is  of  great  importance  from  the  standpoint  of  the  eugenist, 
but  need  not  be  considered  further  in  the  present  connection. 

Suffice  it,  for  the  present,  that  even  the  susceptible  person  is 
susceptible  only  in  a  relative  sense,  and  is  by  no  means  alto- 
gether without  a  defensive  mechanism.  His  chief  danger  may  lie 
in  the  fact  that  his  cells  are  partially  habituated  to  the  presence 
of  this  toxin,  and  therefore  will  not  respond  to  it  actively. 

If  we  inquire  what  can  be  done  to  stimulate  the  defensive 
response,  we  are  at  once  reminded  of  the  methods  that  lead  to 
an  increase  of  the  numbers  of  the  leucocytes  in  the  blood.  The 
ingestion  of  hearty  food,  notably  protein,  leads  to  such  increase. 
Active  exercise  leads  to  such  increase.  Cold  baths  stimulate  such 
increase.  Nourishing  food  in  the  largest  quantities  that  can  be 
assimilated ;  exercise  of  a  fairly  vigorous  type,  and  hydrotherapy 
would  seem  to  be  theoretically  indicated.  Also  fatty  foods  to 
conserve  the  protein,  and  iron  to  facilitate  production  of  hemo- 
globin. No  practical  physician  needs  be  told  that  these  measures 
have  been  shown  empirically  to  be  of  the  greatest  value  in  the 
treatment  of  tuberculosis. 

Recent  experiments  have  shown  that  air  at  very  low  tempera- 


100      THE   PROTEOMORPHIC   THEORY   AND   THE    NEW    MEDICINE 

ture  has  a  stimulative  influence  similar  to  that  of  the  cold  bath. 
This  observation  seems  to  explain  the  familiar  clinical  fact  that 
tuberculosis  may  be  treated  advantageously  in  very  cold  climates. 
The  results  of  sleeping  in  the  open  air  in  an  almost  arctic  tem- 
perature are  familiar  to  clinicians.  The  cold  temperature  is 
probably  as  directly  beneficial  as  the  fresh  air  itself. 

As  to  exercise,  practised  before  the  patient  reaches  a  stage  of 
asthenia  that  makes  it  dangerous,  the  beneficial  results  are  equally 
little  in  doubt.  Mountain  climbing,  with  attendant  fatigue  falling 
just  short  of  extreme  exhaustion,  is  a  recognized  therapeutic 
measure  of  the  utmost  importance.  In  all  probability,  the  climb- 
ing rather  than  the  mountain  air  produces  the  benefit. 

Incidentally  we  may  note,  in  confirmation  of  the  view  of  ery- 
throcytic  activities  here  presented,  that  the  blood  is  thicker  at 
high  altitudes,  so  that  the  red  corpuscles  are  relatively  more 
abundant  and  hence  patrol  the  blood  better ;  but  that  the  total 
amount  of  hemoglobin  is  not  correspondingly  increased  (Viault, 
Abderhalden). 

The  value  of  the  cold  bath  has  long  been  recognized  by  a  few 
astute  clinicians,  who  have  found  it  difficult  to  gain  headway  for 
their  views  partly,  perhaps,  because  the  rationale  of  the  benefits 
to  be  expected  has  hitherto  been  obscure.  The  knowledge  that 
the  cold  bath  directly  stimulates  the  production  of  an  additional 
army  of  leucocytes;  coupled  with  the  belief  that  the  leucocyte 
is  the  pre-eminent  agent  of  immunization  against  the  direct  inva- 
sion of  bacilli,  furnishes  the  all-sufficient  answer.  The  cold  bath 
may  have  other  beneficial  effects,  but  this  one  alone  justifies  its 
use  in  all  bacterial  diseases  in  which  there  is  an  inherent  tendency 
to  defective  leucocytosis. 

A  striking  illustration  of  the  value  of  the  cold  bath  is  fur- 
nished in  the  reports  of  the  Munich  military  hospital,  in  which 
records  of  more  than  eight  thousand  cases  show  that  since  the 
cold  bath  was  used  habitually  in  the  treatment  of  typhoid  fever 
the  mortality  of  that  disease  was  reduced  from  forty-two  per 
cent,  to  three  per  cent. 

As  to  the  matter  of  a  liberal  diet,  there  would  be  no  difference 
of  opinion  in  the  case  of  the  consumptive,  but  opinions  might 
differ,  and  undoubtedly  would  differ,  when  acute  fevers  are  in 
question.  Indeed,  the  old  familiar  rule  to  "starve  a  fever"  has 
been  an  axiom  upon  which  the  average  physician  has  acted  some- 
what persistently.  But  it  has  recently  been  suggested  by  Cole- 
man  that  this  rule  is  perhaps  as  fallacious  as  the  other  rule,  now 
fortunately  abandoned,  that  the  fever  patient  should  be  deprived 
of  water  as  well  as  of  food.  Coleman  reports  gratifying  results 
in  typhoid  fever  cases  in  which  a  liberal  diet  was  provided.  "Not 


THE    PROTEOLYTIC    MECHANISM    IN    OPERATION  101 

only  is  the  course  of  the  disease  favorably  influenced,"  he  says, 
"but  the  condition  of  the  patient  is  vastly  improved." 

And  these  recent  observations  are,  after  all,  only  confirmatory 
of  experiments  conducted  by  Von  Hosslin  more  than  thirty  years 
ago,  which  showed  the  value  of  a  liberal  diet  in  ordinary  fevers. 

If  we  ask  why  a  liberal  diet,  including  proteins,  is  essential 
in  the  treatment  of  fever,  the  answer  is  not  far  to  seek.  Accord- 
ing to  theory,  the  leucocytes  and  red  corpuscles  fight  the  invad- 
ing proteins  and  enzymes  by  constantly  putting  out  chemical  com- 
pounds that  antagonize  them  by  cleaving  their  complex  molecules 
on  one  hand  and  by  combining  them  into  new  and  harmless  asso- 
ciations on  the  other.  But  this  constructive  work  on  the  part 
of  the  corpuscle  implies  the  expenditure  not  merely  of  energy, 
but  of  matter.  And  material  for  this  expenditure  must  in  some 
way  be  found  to  make  up  for  the  constant  depletion. 

The  corpuscles  can  no  more  be  expected  to  perform  their 
work  without  being  supplied  with  fuel  than  can  any  other 
machine. 

Nor  can  new  corpuscles  be  developed  to  fill  the  constantly 
decimated  ranks  without  drawing  on  an  unfailing  supply  of 
proteins.  And  unless  this  material  is  supplied  in  the  pabulum 
that  comes  from  the  outside  world,  usually  through  the  medium 
of  the  intestinal  canal,  it  must  be  found  elsewhere.  And  ob- 
viously the  only  other  source  is  the  body  tissues  themselves.  So 
if  the  defending  hosts  are  not  supplied  with  food  pabulum  from 
without,  they  must  draw  on  the  tissues  of  the  body,  with  a 
weakening  effect.  Hence  the  rapidly  emaciating  effect  of  fevers, 
with  attendant  weakness;  an  effect  largely  avoided  through  use 
of  a  liberal  diet. 

It  will  be  understood,  of  course,  that  the  catabolic  activities  of 
the  leucocyte  and  red  corpuscles,  in  which  complex  protein  mole- 
cules are  constantly  cleaved  to  smaller  molecules  and  arranged 
in  new  combinations,  must  be  attended  by  a  constant  liberation 
of  heat.  So  the  fever  itself  is  in  part  an  evidence  of  the  activ- 
ities of  the  corpuscles.  And  liberal  feeding,  provided  the  food 
is  assimilated,  may  unquestionably  tend  to  enhance  the  fever. 

But  the  modern  clinician  does  not  regard  fever  as  in  itself 
necessarily  disadvantageous  to  the  patient.  On  the  contrary, 
he  associates  it  with  the  immunizing  and  curative  processes  in 
the  body.  So  he  does  not  regard  a  rise  in  temperature  as  neces- 
sarily an  evil.  He  knows  that  the  phagocytic  activities  of  the 
leucocytes  are  greatly  accelerated  when  the  temperature  is  high; 
the  leucocytes  have  been  observed  at  increased  temperatures  to 
"dart  about  like  bees  around  a  hive."  It  may  reasonably  be 
inferred  that  the  chemical  activities  of  all  the  immunizing  agents 
are  correspondingly  accelerated. 


102      THE   PROTEOMORPHIC   THEORY   AND  THE    NEW    MEDICINE 

Nevertheless  there  are  dangers  in  excessive  temperature,  if 
for  no  other  reason  because  tissues  that  it  is  essential  to  con- 
serve are  also  stimulated  thereby  to  unwonted  activity.  So  it  is 
highly  desirable  from  time  to  time  to  accelerate  the  removal 
from  the  body  of  the  excessive  heat  due  to  the  chemical  activ- 
ities. And,  of  course,  the  best  practical  means  of  accomplishing 
this  is  the  cold  bath. 

The  idea  of  giving  a  fever  patient  liberal  potations  of  water, 
feeding  him  freely  with  nourishing  foods,  and  from  time  to 
time  plunging  him  into  cold  baths  or  swathing  him  in  cold  packs 
would  have  come  very  near  to  giving  an  apoplectic  shock  to  the 
best  clinicians  of  a  century  ago.  But  nowadays  such  procedures 
have  the  fullest  experimental  or  clinical  warrant,  and  find  expla- 
nation in  the  data  of  physiological  chemistry. 

It  is  probable,  however,  that  comparatively  few  clinicians 
among  these  who  use  the  cold  bath  habitually  in  fever  cases, 
and  recognize  its  value  in  the  direct  reduction  of  temperature, 
take  cognizance  also  of  its  significance  in  stimulating  the  cyto- 
genic  organs  to  the  production  of  new  hosts  of  germ  destroyers. 
Yet  it  is  probable  that  the  latter  is  by  no.  means  the  least  of  the 
services  performed  by  the  cold  bath. 

It  is  a  little  difficult  to  accustom  one's  self  to  the  idea  that 
there  is  no  necessary  connection  between  the  degree  of  fever 
and  the  virulence  of  intoxication.  But  the  truth  of  this  propo- 
sition is  suggested  by  the  familiar  observation  that  infants  often 
show  a  high  temperature  when  their  maladies  are  comparatively 
mild.  And  it  receives  experimental  demonstration  through  the 
observations  of  Vaughan  and  others  to  the  effect  that  small  doses 
of  a  protein  poison  may  cause  a  rise  of  temperature  in  animals 
where  far  larger  doses  of  the  same  toxin  produce  no  fever,  but 
may  even  cause  a  fall  in  temperature. 

Vaughan  very  justly  refers  to  this  as  a  puzzling  and  not  clearly 
explicable  fact.  A  conceivable  explanation  might  be  that  small 
doses  stimulate  the  defensive  leucocytic  mechanism,  while  large 
doses  act  with  such  suddenness  and  violence  as  to  paralyze  them ; 
just  as  they  sometimes  seem  to  be  helpless  when  they  have  in- 
gested a  large  number  of  toxic  bacteria.  It  should  be  recalled 
that  the  introduction  of  these  large  doses  of  foreign  proteins 
directly  into  the  vascular  system  is  a  phenomenon  that  would  be 
of  exceeding  rare  occurrence  outside  the  laboratory.  The  fang 
of  a  serpent  is  about  the  only  mechanism  in  the  natural  world 
that  would  be  capable  of  introducing  a  foreign  protein  in  quan- 
tity into  the  animal  system.  So  the  defensive  mechanism  has 
not  often  been  called  on  to  reckon  with  this  contingency,  and 
it  cannot  deal  effectively  with  excessive  doses  of  toxic  proteids. 

But,  however  explained,  these  laboratory  experiments  are  of 


THE    PROTEOLYTIC    MECHANISM    IN   OPERATION  103 

great  value  in  teaching  the  clinician  that  he  must  not  depend 
too  fully  on  his  clinical  thermometer  as  a  guide  to  the  virulence 
of  disease. 

As  to  pharmaceutical  agents  calculated  to  stimulate  the  activ- 
ities of  the  cytogenic  system,  mention  was  made  in  the  original 
presentation  of  the  Proteomorphic  thesis,  of  secretin,  of  thyroid 
extract,  of  powdered  spleen,  and  of  bone  marrow.  Doubtless 
these  agents  have  a  measure  of  utility,  but  in  the  light  of  recent 
experience  they  assume  an  altogether  subordinate  role.  The 
parenteral  injection  of  non-toxic  proteins  has  been  shown  to 
offer  therapeutic  possibilities  scarcely  more  than  adumbrated  by 
any  stimuli  to  the  cytogenic  apparatus  hitherto  known.  These 
possibilities  are  forecast  in  the  general  treatment  of  the  theory 
of  antigenic  response  in  the  original  presentation  of  the  Pro- 
teomorphic theory. 

The  details  of  their  application,  through  the  development  of 
Proteal  therapy,  will  form  the  subject  matter  of  most  of  the 
succeeding  chapters  of  this  book. 

SERUMS,  VACCINES,  AND  DIRECT  CYTO-THERAPY 

Of  specific  serum  and  vaccine  therapy  in  general  I  shall  speak 
only  in  the  most  general  way,  although  reference  to  the  non- 
specific elements  always  necessarily  involved  will  be  made  in 
another  connection.  By  way  of  anticipation,  however,  there 
are  one  or  two  aspects  of  the  subject  that  may  advantageously 
be  given  brief  consideration  here,  from  the  standpoint  of  the 
Proteomorphic  theory. 

Consider,  for  example,  the  observation  of  Dr.  W.  H.  Park,  to 
the  effect  that  when  a  horse  having  a  strongly  antitoxic  blood  is 
injected  intravenously  with  a  definite  amount  of  toxin,  very 
little  production  of  antitoxin  takes  place,  because  the  toxin  is 
neutralized  by  the  antitoxin  in  the  blood,  whereas  the  same 
amount  injected  in  scattered  spots  subcutaneously  will  produce  a 
large  amount  of  antitoxin.  Dr.  Park  argues,  logically  enough, 
that  such  portions  of  the  subcutaneously  injected  toxin  as  come 
into  the  blood  stream  will  meet  the  same  fate  as  that  injected 
intravenously.  He  concluded,  therefore,  that  some  or  all  of  the 
cells  in  the  area  in  the  subcutaneous  tissues  that  the  toxin  reaches 
must  take  part  in  producing  antitoxin. 

This  conclusion  is  obviously  in  harmony  with  the  Proteomor- 
phic theory,  which  postulates  that  body-cells  of  many  types  may 
on  occasion  respond  to  the  invasion  of  toxins  of  the  polypeptid 
order  of  chemical  complexity.  It  should  be  recalled,  however, 
that  white  and  red  corpuscles  are  everywhere  within  reach,  in 
more  or  less  static  capillaries  and  tissue  fluids,  and  that  their 


104      THE   PROTEOMORPHIC  THEORY   AND  THE   NEW    MEDICINE 

services  may  have  been  available,  even  though  the  injection  was 
not  made  directly  into  the  blood  stream. 

Again  in  Sir  Almroth  Wright's  application  of  vaccine  therapy 
to  localized  infections  already  in  being,  such  as  boils,  and  even 
to  general  infections,  including  typhoid  fever,  the  injection  is 
usually  subcutaneous  or  intramuscular,  not  intravenous,  but  it 
is  obvious  that  the  leucocytes  residing  at  the  moment  in  the 
static  tissue  fluids  and  lymph  spaces  are  brought  directly  into 
contact  with  the  invading  bacteria  (in  this  case  dead,  but  laden 
with  their  foreign  proteid).  They  are  seen  to  accumulate  and 
to  attack  the  dead  bacilli  actively,  and  we  can  hardly  doubt  that 
they  are  directly  stimulated  to  send  out  antidotes — complement, 
opsonin,  bacteriolysin — that  presently  percolate  into  the  general 
blood  stream  and  are  carried  to  the  special  tissues  where  the 
invasion  of  living  germs  is  taking  place. 

In  this  case  the  locally  injected  germs  are  unquestionably  at- 
tacked and  largely  engulfed  by  the  local  garrisons  of  leucocytes, 
and  it  is  difficult  to  conceive  what  other  agent  can  be  responsible 
for  the  secretion  of  the  antibodies  with  which  the  blood  presently 
becomes  infused. 

Although  it  seems  almost  unavoidable  to  conclude,  in  such  a 
case  as  this,  that  the  white  blood  corpuscle  is  the  agent  of  anti- 
body production,  where  protein  poisons  are  in  question,  yet  the 
conclusion,  after  all,  is  inferential  only.  Some  remarkable  ex- 
periments have  recently  been  made  by  J.  W.  Vaughan,  however, 
in  which  the  genesis  of  specific  enzymes  in  the  body  of  the  leuco- 
cytes in  response  to  protein  poisoning,  is  demonstrated. 

In  these  experiments,  as  recorded  by  Victor  C.  Vaughan,  the 
inoculation  of  sheep  or  rabbits  with  finely  ground  cancer  tissue 
led  to  the  rapid  increase  of  large  mononuclear  leucocytes  in  the 
blood,  until  they  reached  twenty-five  per  cent,  or  more  of  the 
entire  leucocytic  population.  The  animal  is  then  bled,  the  blood 
is  laked  with  acetic  acid,  and  the  leucocytes  are  collected  in  a 
centrifuge.  They  are  rubbed  with  sterile  sand  in  salt  solution 
and  passed  through  a  Berkefeld  filter. 

It  is  found  then  that  the  filtrate  contains  the  specific  proteolytic 
ferment  which  splits  up  cancer  cells. 

"This  is  shown  by  incubating  it  with  cancer  cells,  when  the 
poisonous  portion  of  the  protein  molecule  is  freed,  as  is  shown 
by  the  fact  that  when  injected  in  the  fresh  rabbit  it  causes  sud- 
den death.  Incubated  with  other  proteins,  the  leucocytic  extract 
liberates  no  poison.  This  leucocyte  extract  when  injected  in 
certain  amount  directly  into  cancer  tissue  produces  anaphylac- 
tic  shock." 

The  experiment  led  the  elder  Vaughan  to  conclude  that  "this 
work  seems  to  indicate  that  the  specific  enzyme  for  cancer  cells 


THE    PROTEOLYTIC    MECHANISM    IN    OPERATION  105 

is  furnished  by  the  large  mononuclear  leucocyte."  Another  in- 
terpretation is  possible,  as  I  shall  show  presently,  but  the  experi- 
ment justifies  the  conclusion  "that  in  work  of  this  kind  lies  a 
promise  of  at  least  partially  insulating  the  anaphylactic  enzymes 
and  studying  their  effects." 

"Anaphylactic  enzymes,"  it  will  be  understood,  is  the  term 
used  by  Vaughan  to  describe  the  so-called  antibodies  put  out  in 
response  to  foreign  proteins,  about  which  we  have  all  along 
been  speaking. 

This  experiment  certainly  shows  that  in  some  cases  the  leu- 
cocyte may  be  the  agent  of  origin,  or  at  least  of  transfer,  of 
the  antibodies  directed  against  poisons.  It  should  be  added,  how- 
ever, that  the  elder  Vaughan  does  not  ascribe  this  function  ex- 
clusively to  the  leucocytes,  for  he  expressly  states  in  another 
connection  that  it  is  possible  that  the  protective  enzymes  are 
formed  by  different  cells  according  to  the  "sensitizer"  (i.e.,  the 
proteid  toxin)  used — a  view  obviously  in  harmony  with  the  pro- 
teomorphic  theory,  though  far  too  general  to  be  cited  as  spe- 
cifically supporting  the  theory. 

In  the  original  presentation  of  the  Proteomorphic  theory  it 
was  noted,  in  pursuance  of  this  aspect  of  the  subject,  that 
Vaughan  was  then  testing  his  extract  of  mononuclear  leucocytes 
in  the  treatment  of  cancer,  and  the  following  comment  was 
made,  which  has  peculiar  interest  in  the  light  of  more  recent 
developments :  "Whatever  the  immediate  results  of  this  par- 
ticular test,  there  is  every  reason  to  hope  that  the  method  in- 
augurated, in  which  the  leucocytes  are  directly  looked  to  for  the 
production  of  immunizing  enzymes,  will  be  generalized  and  given 
an  important  place  in  therapeutic  procedure  in  the  near  future. 
It  is  a  short  step  from  the  clear  conception  that  the  leucocytes 
are  the  chief  agents  in  the  producing  of  immunizing  ferments 
to  the  direct  utilization  of  the  leucocytes  themselves  in  thera- 
peutic procedure. 

"That  an  antidote  thus  prepared  may  have  marked  advantages 
over  an  antitoxic  serum  is  clearly  suggested  in  the  work  of 
Vaughan  just  referred  to.  For  he  found  it  impossible  to  use 
the  serum  of  a  'sensitized'  animal,  because,  in  the  first  place, 
repeated  injections  of  the  serum  caused  albuminuria ;  and,  in 
the  second  place,  they  'sensitized*  to  the  proteins  of  the  serum. 
The  leucocytic  extract  also  'sensitizes'  to  the  blood  serum,  until 
it  is  passed  through  a  Berkefeld  filter,  after  which  it  is  innocu- 
ous. All  of  which  may  readily  be  interpreted  in  terms  of  the 
Proteomorphic  theory. 

"Here,  then,  is  at  least  a  strong  suggestion  of  the  possibility 
of  producing  antibodies  directly  from  the  filtered  bodies  of  the 
leucocytes,  and  avoiding  the  danger  of  serum  disease  which  is 


106      THE   PROTEOMORPHIC   THEORY   AND  THE   NEW    MEDICINE 

well  recognized  as  attendant  on  the  present  method  of  serum 
therapy  and  which  sometimes  has  such  alarming  results." 

I  wrote  these  words  in  September,  1914.  Following  them  I 
presented  a  recapitulatory  summary  of  the  essentials  of  the 
Proteomorphic  theory,  concluding  with  these  words: 

"The  general  theory  of  the  action  of  the  cytogenic  system 
above  outlined  finds  support  in  clinical  observations  of  disease 
and  in  empirical  therapy;  and  the  theory  itself  gives  important 
clues  to  the  scientific  application  of  old  and  new  therapeutic 
measures,  including  an  extension  of  serum-therapy  and  vaccine- 
therapy  and  the  development  of  a  new  cyto-therapy. 

"Such,  then,  are  some  of  the  salient  aspects  of  the  Proteo- 
morphic theory  of  immunization ;  a  theory  which  postulates  the 
cytogenic  system  as  the  chief  immunizing  mechanism,  and  its 
daughter  cells,  the  leucocytes  and  red  corpuscles,  as  the  active 
direct  agents  in  carrying  out  the  beneficent  functions  of  that 
mechanism. 

"It  is  not  claimed  that  a  complete  demonstration  of  the  truth 
of  this  theory  in  all  its  aspects  has  been  presented,  nor  that 
such  demonstration  is  possible  with  data  at  present  available. 
Nor  can  it  be  supposed  that  all  parts  of  so  novel  a  theory  have 
been  correctly  conceived.  Yet,  even  as  presented,  it  would  appear 
that  the  theory  throws  light  into  a  good  many  dark  places  of 
the  realms  of  physiology  and  pathology. 

"In  any  event,  I  feel  that  the  fundamental  concept  of  the 
theory  has  been  made  sufficiently  plausible  to  justify,  and  in- 
deed to  demand,  a  far  larger  share  of  attention  for  the  leucocyte 
and  the  red  corpuscle  on  the  part  of  bacteriologist,  pathologist, 
and  practicing  physician  than  has  hitherto  been  accorded  these 
small  but  highly  important  bodies." 

The  story  of  the  development  of  the  "new  cyto-therapy"  thus 
adumbrated,  under  guidance  of  the  Proteomorphic  theory,  has 
been  told  in  part  on  earlier  pages  of  this  volume,  and  will  be 
further  elaborated  in  succeeding  chapters. 


CHAPTER  III 

THE  DISCOVERY  OF  THE  PROTEIN  PRINCIPLE  IN 
THERAPEUTICS 

Shortly  after  the  first  publication  of  the  Proteomorphic  Theory 
(American  Medicine,  October  and  November,  1914),  I  was  in 
Baltimore  and  had  opportunity  at  Dr.  Howard  Kelly's  private 
sanitorium  to  see  a  number  of  cancer  cases  undergoing  radium 
treatment.  I  was  also  shown  photographs  some  of  which  re- 
vealed really  spectacular  modifications  of  malignant  growths 
under  influence  of  radium,  and  I  received  first-hand  accounts, 
from  physicians  not  directly  connected  with  the  work,  of  cases 
in  which  cancerous  growths  had  magically  disappeared  appar- 
ently as  a  direct  result  of  the  application  of  radium. 

These  observations  interested  me  profoundly,  and  from  many 
points  of  view.  Not  long  before  I  had  visited  Professor  Ernest 
Rutherford  in  his  famous  laboratory  at  Manchester,  and  had 
been  permitted  to  study  at  first  hand  his  radium  apparatus,  and 
to  observe  his  fascinating  experiments.  I  had  visited  Sir  J.  J. 
Thompson  at  the  Cavandish  Laboratory  in  Cambridge,  at  the 
time  when  he  was  making  his  first  photographs  of  atoms  in  the 
vacuum  chamber.  I  had  visited  Lenard,  the  precursor  of  Roent- 
gen, at  Freiburg ;  and  Ostwald  at  his  home  in  Grossbothen ;  and 
Arrhenius  at  the  Nobel  Institute  in  Stockholm;  and  Zeeman  in 
his  wonderful  laboratory  at  Amsterdam;  and  had  discussed  the 
alluring  problems  of  the  ultimate  constitution  of  matter, 
the  relations  of  matter  and  energy,  the  character  of  chemical 
action  and  electrical  action,  and  kindred  subjects  suggested  by 
the  different  yet  closely  allied  discoveries  for  which  these  men 
are  famous. 

I  had  also  visited  and  talked  with  a  group  of  discoverers 
in  the  biological  field,  and  similarly  attempted  to  correlate  their 
observations — for  example,  Metchnikoff,  at  the  Pasteur  Insti- 
tute in  Paris,  who  was  then  studying  conditions  in  the  alimen- 
tary tract  in  their  relation  to  health  and  longevity;  Ehrlich,  at 
his  Frankfort  Institution,  who  had  just  given  the  world  salvarsan, 
and  thereby  revived  hope  in  specific  chemo-therapy ;  Sir  Aim- 
wroth  Wright,  at  St.  Mary's  Hospital  in  London,  who  was 
actively  elaborating  the  theory  and  practice  of  autogenous  vac- 
cine therapy,  and  venturing  into  another  new  field  in  the  attempt 
to  combat  hay  fever  with  pollin  extracts ;  and  Professor  George 
F.  H.  Nuttall,  Quick  Professor  Biology  at  Cambridge  Univer- 
sity, whose  fascinating  work  with  the  precipitins,  through  which 

107 


108      THE    PROTEOMORPHIC   THEORY   AND  THE    NEW    MEDICINE 

he  had  tested  the  genetic  relationship  of  hundreds  of  species  of 
animals,  had  recently  won  him  Fellowship  in  the  Royal  Society — 
a  distinction  shared,  I  believe,  by  no  other  American. 

With  the  work  of  these  men  I  had,  of  course,  long  been 
familiar.  Some  of  the  men  I  had  known  for  years,  and  visited 
on  previous  occasions.  But  at  this  time  I  was  making  an  espe- 
cial effort  to  correlate  the  new  advances  along  different  lines  of 
science  in  the  fields  of  physics,  chemistry,  and  biology.  A  little 
later  I  sought,  through  correspondence,  the  opinions  of  a  thou- 
sand leading  men  of  science,  actual  workers  in  one  field  or  an- 
other, as  to  what,  in  their  judgment,  was  the  most  important 
unexplored  or  half-explored  field  just  ahead.  By  co-ordinating 
these  diversified  opinions,  I  thought  to  attain  a  clearer  view  than 
had  hitherto  been  possible  of  the  trend  of  scientific  thought  in 
our  day  and  the  probable  eventualities  of  the  new  scientific  era 
on  the  threshold  of  which  we  stand. 

It  was  these  studies,  doubtless,  combined  with  the  earlier  in- 
vestigations that  had  found  expression  in  my  History  of  Science, 
that  made  possible  the  crystallization  of  ideas  in  my  mind  rep- 
resented by  the  Proteomorphic  Theory.  The  actual  textual  for- 
mulations of  that  theory  at  the  particular  time  when  it  was 
written  came  about  through  the  accident  of  my  being  asked  to 
make  a  summary  of  existing  theories  of  immunization.  The 
mental  co-ordination  through  which  the  new  and  in  a  sense  revo- 
lutionary tenets  of  the  Proteomorphic  .Theory  flashed  into  my 
mind  eventuated,  rather  curiously,  one  evening  as  I  sat  at  din- 
ner with  my  daughter  in  a  little  restaurant  down  in  llth  Street. 
The  dictating  of  the  twenty-five  thousand  words  of  copy  com- 
prised in  the  presentation  of  the  theory  in  American  Medicine 
was  a  tour  de  force  begun  and  completed  in  the  leisure  hours 
of  three  or  four  consecutive  days.*  But  the  connotations  of  the 

*I  would  not  seem  to  imply  that  the  writing  of  this  amount  of  matter 
in  the  time  mentioned  constitutes  an  unusual  task.  A  few  months  before 
the  Proteomorphic  theory  was  written  I  had  dictated  more  than  half  a 
million  words  of  finished  manuscript  (making  eleven  fair-sized  volumes) 
and  turned  the  manuscript  over  to  the  printer  in  a  period  of  fifty  con- 
secutive days.  On  almost  numberless  occasions  I  have  written  from 
twelve  thousand  to  fifteen  thousand  words  of  finished  manuscript  per  day 
for  days  together.  One  of  my  large  books  was  begun  on  Monday  morning 
and  finished  Saturday  night  of  the  same  week.  Another  (Volume  I  of  my 
History  of  Science)  was  produced  in  the  midst  of  exacting  duties  of  a 
different  character  by  dictating  one  hour  daily  (eight  to  nine  in  th< 
morning)  for  twenty  consecutive  days.  I  mention  these  incidents  tc 
illustrate  an  habitual  tendency  to  concentrated  mental  action,  in  explana- 
tion of  the  seeming  anomaly  that  so  comprehensive  and  even  revolutionarj 
a  doctrine  as  that  comprised  in  the  Proteomorphic  theory  should  have 
been  produced  rather  as  a  mental  pastime  than  as  a  fixed  task.  I  majl 
add,  however,  that  the  aftermath  of  the  "mental  pastime"  in  question 
has  involved  me  in  a  series  of  laborious  investigations,  of  which  this 
volume  gives  some  intimations,  that  will  probably  occupy  a  large  part 
of  my  time  for  the  remainder  of  my  life. 


DISCOVERY   OF   PROTEIN    PRINCIPLE   IN    THERAPEUTICS        109 

theory,  and  the  mental  associations  that  made  its  elaboration 
possible,  represented  a  lifetime  of  study;  and  the  sequential  de- 
velopments, to  which  I  am  about  to  refer,  were  equally  con- 
ditioned on  antecedent  knowledge  acquired  through  years  of  in- 
vestigation. It  is  in  this  connection  that  I  call  to  mind  the 
otherwise  unrelated  incidents  just  cited. 

In  particular,  I  would  recall  that  the  thing  that  impressed  me 
most  in  the  visit  to  Ehrlich,  above  mentioned,  was  the  room  in 
his  laboratory  where  endless  series  of  glass  jars  contained  can- 
cerous mice.  Ehrlich  himself  at  the  moment  was  all  enthused 
over  his  tentative  success  with  salvarsan,  and  he  made  but  inci- 
dental reference  to  the  cancer  mice,  but  I  felt  that  this  was  the 
problem  that  would  next  engage  his  attention — a  problem,  in- 
deed, that  had  been  interrupted  by  the  other  studies.  With 
peculiar  interest,  then,  I  learned  a  little  later  of  the  experiment 
in  which  he  had  attained  at  least  tentative  results  in  the  devel- 
opment of  a  chemical  combination,  including  selinium,  that  ap- 
peared to  have  a  selective  action  on  cancer  cells ;  a  work  dupli- 
cated, independently,  I  believe,  by  Wassermann,  in  Berlin. 

These  observations,  and  the  still  newer  work  of  Wassermann, 
in  which  he  had  endeavored  to  diagnose  the  presence  of  cancer 
by  tests  applied  to  the  blood,  were  fresh  in  my  mind  when  I 
observed  the  patients,  and  studied  the  photographs,  at  Dr.  Kelly's 
sanitorium  there  in  Baltimore.  I  had  also  in  mind  the  recently 
reported  experiments  of  Dr.  Leo  Loeb  with  colloidal  copper  in 
the  treatment  of  cancer.  And  I  was,  of  course,  familiar  with 
various  tentatives  in  cancer  treatment  that  had  been  made  with 
biological  products,  as  admirably  summarized  in  Dr.  Bainbridge's 
book  of  which  just  at  this  time  I  received  a  presentation  copy 
from  the  author.  In  particular  I  had  followed  with  interest  the 
work  of  Hodenpyl,  partly  because  I  chanced  to  know  personally 
the  patient  from  whom  the  ascitic  fluid  used  by  him  with  such 
thought-provocative  results  was  removed. 

And  as  I  linked  and  co-ordinated  these  various  items  of  knowl- 
edge, the  thought  that  was  paramount  in  my  mind  was  that,  be- 
yond preadventure,  it  had  been  demonstrated  that  the  cells  of  a 
malignant  neoplasm,  notwithstanding  their  similarity  to  normal 
cells,  have  essential  differences  that  bring  them  within  the  pos- 
sibility of  selective  action  on  the  part  of  physical  or  chemical 
agencies.  The  fact  that  all  the  methods  of  practically  treating 
cancer  used  hitherto  had  proved  only  tentative  or  utterly  dis- 
appointing; the  fact  that  the  cancer  mass  seemingly  dispelled 
by  radium  treatment  might  recur  and  grow  with  renewed  and 
fatal  activity — these  facts  seemed  to  me  altogether  subordinate 
to  the  great  central  fact  that  the  cancer  cell  could,  in  some 
instances,  be  caused  to  undergo  seemingly  autolysis  through  the 


110      THE   PROTEOMORPHIC  THEORY   AND  THE    NEW    MEDICINE 

application  of  agencies  that  were  not  necessarily  destructive  of 
the  normal  tissues  subjacent  to  the  abnormal  growth. 

This  possibility  being  demonstrated,  it  seemed  to  me  that  the 
first  great  step  toward  the  ultimate  successful  issue  of  the  con- 
test with  cancer  had  been  taken. 

It  appeared  to  me,  however,  that  radium  therapy,  as  applied 
to  cancer — and  the  allied  X-ray  treatment  which  I  had  also 
investigated — was  subject  to  one  almost  insuperable  difficulty. 
It  was  hard  to  conceive  how  a  method  could  be  devised  through 
which  the  application  of  the  disruptive  rays  could  be  brought 
to  bear  on  the  cancer  cells  without  bringing  an  influence  on  the 
cells  of  healthy  subjacent  tissues ;  and  there  was  ample  clinical 
evidence  that  if  this  influence  was  carried  beyond  a  certain 
stage  injury  resulted  to  the  healthy  cells  no  less  than  to  the 
abnormal  ones.  The  fair  inference  seems  to  be  that  the  cancer 
cells  are  of  somewhat  less  stable  constitution;  that  they,  there- 
fore, yield  more  readily  to  the  disruptive  influence  of  the  radia- 
tion; but  that  the  difference  between  these  cells  and  the  normal 
cells  in  this  regard  is  a  difference  of  degree  and  not  a  differ- 
ence of  kind.  Such  being  the  case,  there  is  an  obvious  obstacle 
in  the  use  of  radium  or  the  X-ray,  which  by  no  means  bars 
these  agents  from  usefulness,  but  which  suggests,  as  it  seems 
to  me,  that  they  do  not  give  promise  of  ultimate  ideal  solution 
of  the  problem. 

The  ideal  would  be  a  chemical  agent,  biological  or  other,  that 
had  selective  chemical  affinity  for  the  cancer  cell,  with  capacity 
to  effect  disruptive  activities,  somewhat  as  salvarsan  seemingly 
has  selective  affinity  for  the  spirochaete  of  syphilis. 

In  particular,  at  this  time,  my  mind  dwelt  on  the  experiment 
of  Vaughan,  with  a  brief  statement  of  which  the  original  presen- 
tation of  the  Proteomorphic  Theory  had  been  concluded,  which 
showed  that  the  large  mononuclear  leucocyte  produces  or  con- 
tains enzymes  capable  of  splitting  up  cancer  cells.  In  the  con- 
cluding paragraph  of  the  Proteomorphic  Theory,  as  originally 
published,  I  suggested  the  possibility  of  producing  antibodies 
from  the  bodies  of  leucocytes ;  and  I  had  in  mind,  naturally, 
the  possible  application  of  such  enzymes  in  the  treatment  of 
cancer  (it  was  well  known  that  Vaughan  was  working  prac- 
tically along  these  lines),  and  also  the  more  general  application 
of  the  method  implied  in  a  predicted  "extension  of  serum  therapy 
and  vaccine  therapy  and  the  development  of  a  new  cyto-therapy." 

That  the  suggested  new  therapy  involved  the  use  of  meas- 
ures to  increase  the  numbers  of  corpuscles,  and  stimulate  their 
enzymic  activities,  was  everywhere  implied,  and  moreover  was 
explicitly  stated  in  the  discussion  of  agents  calculated  to  produce 
this  effect;  but  the  simple  method  of  evoking  a  corpuscular  re- 
sponse by  parenterally  introducing  foreign  proteins  as  such  did 


DISCOVERY   OF   PROTEIN    PRINCIPLE   IN    THERAPEUTICS        111 

not  occur  to  me  until  later — although  the  idea  lies  so  near  to 
hand  that,  looking  back,  it  would  seem  that  it  must  inevitably 
occur  to  any  one  who  grasps  the  fundamental  features  of  the 
Proteomorphic  Theory.  But  here,  as  so  often  elsewhere  in  the 
field  of  discovery,  the  retrospectively  obvious  may  not  be  obvious 
to  all  from  the  contemporaneous  standpoint. 

Nevertheless  the  idea  was  apparently  very  close  to  the  sur- 
face of  my  mind,  for  it  came  into  clear  view,  as  a  vivid  reality, 
a  little  later,  and  was  given  concrete  and  tangible  expression  in 
the  paper  that  I  published  in  the  New  York  Medical  Journal, 
October  2,  1915 — just  a  year  after  the  original  publication  of 
the  Proteomorphic  Theory. 

The  specific  observations  that  led  to  the  clear  realization  and 
application  of  the  Proteomorphic  principle  had  to  do  with  a 
series  of  cases  of  cancer,  part  of  which  had  come  under  my 
direct  personal  observation,  and  the  remainder  under  observa- 
tion at  second  hand,  so  to  speak,  through  personal  correspond- 
ence with  the  physicians  who  treated  them.  The  treatment  con- 
sisted of  the  hypodermic  injection  of  a  vegetable  extract,  the 
nature  of  which  was  not  at  first  very  clearly  divulged,  but  which 
was  ultimately  known  to  be  produced  by  macerating  a  dozen 
powdered  plant  substances  in  salt  solution  or  in  alcohol.  The 
substances  in  question,  as  ultimately  revealed,  were  the  follow- 
ing: Menyanthes  trifoliata,  buckbean  (leaves);  Melilotus  offici- 
nalis,  sweet  clover  (leaves)  ;  Mentha  crispa,  mint  (leaves)  ;  Bras- 
sica  alba,  mustard  (seed)  ;  Anemone  hepatica,  liver  leaf  (leaves)  ; 
Viola  tricolor,  pansy  (flowers  and  leaves) ;  Anthemis  nobilis, 
camomile  (leaves);  Citrullus  Colocynthis,  colocynth  (fruit); 
Quassia  amara,  quassia  (wood)  ;  Urtica  diocia,  nettle  (whole 
plant  except  root)  ;  Rheum  officinale,  rhubarb  (root)  ;  and  Hys- 
sopus  officinalis,  hedge  hyssop  (whole  plant  except  root). 

The  formula  for  this  bizarre  compound,  of  unrevealed  origin 
(and  now  having  only  historical  interest),  had  been  brought  to 
this  country  by  a  Hungarian  layman  and  used  originally  as  a 
poultice  in  the  treatment  of  superficial  epitheliomas  and  carci- 
nomas. The  extract  in  question,  made  at  the  instance  of  some 
New  York  physicians  who  became  interested  in  the  matter,  was 
used  hypodermically,  and  at  first  injected  directly  into  the  can- 
cer mass,  the  observed  effect  being  supposed  to  be  local. 

My  attention  was  called  to  the  matter  in  February,  1915,  soon 
after  I  had  observed  at  first  hand  the  effects  of  radium  in  the 
treatment  of  cancer  in  Dr.  Kelly's  sanitorium  as  above  related, 
and  at  a  time  when  my  mind  was  actively  engaged  in  consid- 
ering various  aspects  of  the  cancer  problem,  and  of  the  pos- 
sible application  of  the  Proteomorphic  Theory.  It  is  speaking 
within  bounds  to  say  that  I  was  profoundly  impressed  with  what 
I  saw  of  cases  under  treatment  with  the  vegetable  extract  at 


112      THE   PROTEOMORPHIC  THEORY   AND  THE   NEW    MEDICINE 

the  Polyclinic  Hospital  in  New  York.  The  clinical  results,  par- 
ticularly in  a  case  of  cancer  of  the  rectum  and  a  case  of  hyper- 
nephroma,  struck  me  as  spectacular  and  in  the  highest  degree 
thought-provocative. 

But  I  was  impressed  also  with  the  observation  that — in  these 
cases  and  in  various  others — there  appeared  to  be  a  congested 
condition  in  the  region  of  the  tumor  masses,  involving  both 
white  corpuscles  and  red,  that  was  at  least  inferentially  asso- 
ciated with  the  autolytic  process. 

Meantime  the  action  of  the  extract  was  not  that  of  an  escha- 
rotic.  This  was  fairly  obvious  even  at  the  outset,  when  injec- 
tion was  made  directly  into  the  tumor  masses;  but  it  became 
demonstrative  when  it  was  found  a  little  later  that  the  hypo- 
dermic injection  could  be  made  into  distant  regions  of  the  body 
— say,  the  upper  arm — with  apparently  the  same  results  in 
localized  action  on  a  tumor  of  the  breast,  the  uteras,  the  stom- 
ach, or  other  region.  This  seemed  to  imply  a  selective  action  as 
between  cancer  cells  and  normal  cells ;  and  the  observations  on 
the  blood  appeared  to  justify  the  inference  that  the  corpuscles 
were  the  effective  agents  through  which  the  selection  came  about. 

Such,  at  least,  was  my  own  inference,  biased  as  I  naturally  was 
by  what  may  be  called  the  Proteomorphic  point  of  view. 

Coupled  with  the  collateral  observations  outlined  above,  the 
matter  seemed  to  be  of  sufficient  importance  to  merit  very  care- 
ful investigation.  I  made  such  investigations  in  the  offices  of 
the  New  York  physicians  who  were  applying  the  treatment,  and 
through  correspondence  with  numerous  others.  I  also  visited  a 
physician  in  a  neighboring  city,  who  had  twenty-five  or  thirty 
cases  under  treatment,  carefully  inspecting  the  cases.  In  the 
aggregate,  the  cases  that  came  under  my  personal  observation 
in  the  half  year  following  the  first  observations  numbered  about 
three  hundred.  The  reports  from  other  physicians  brought  the 
number  to  upward  of  a  thousand.  And  the  conclusion  forced 
upon  me  was  that  certain  definite  and  tangible  results  attended 
the  administration  of  the  extract.  They  were  results  closely  sim- 
ilar to  those  that  had  been  attained  by  the  use  of  various  and 
sundry  of  the  biological  extracts  above  referred  to ;  and  sub- 
stantially identical  with  those  attained  by  the  workers  at  the 
Crocker  Research  Fund  Institution  with  animal  extracts,  to 
which  fuller  reference  will  be  made  in  another  connection.  But 
the  method  had  merits  over  the  antecedent  ones  in  question  in 
that  the  extract  used  could  be  readily  prepared,  and  lacked  the 
toxicity  that  characterized  some  of  the  others — for  example, 
the  bacterial  extract  known  as  Coley's  fluid,  the  efficacy  of 
which,  in  some  cases  of  sarcoma,  appears  to  be  beyond  question. 

When  the  extract  was  first  brought  to  my  attention  I  was 


DISCOVERY   OF   PROTEIN    PRINCIPLE   IN    THERAPEUTICS        113 

told  that  no  one  had  any  very  clear  notion  as  to  how  it  op- 
erated, but  that  it  was  known  to  contain  chlorophyll,  and  that 
its  action  was  supposed  to  be  due  either  to  this  substance  or  to 
some  unknown  agent  of  the  nature  of  a  vitamine.  It  was  not 
until  about  six  months  later  that  I  learned  the  method  of  prep- 
aration of  the  extract;  then  the  fact  was  revealed  that  it  con- 
tained vegetable  proteins  in  solution.  Long  before  this  I  had 
freely  expressed  the  opinion  that  there  was  nothing  specific  about 
the  particular  vegetable  compound  used  to  make  the  extract,  and 
had  predicted  that  it  would  be  possible  to  make  extracts  from 
numberless  other  vegetables  that  would  be  equally  effective. 
This  prophecy  was  in  part  based  on  the  supposition  that  chloro- 
phyll was  the  active  agent  involved. 

But  when  I  learned  that  the  extract  contained  vegetable  pro- 
teins, a  clear  conception  of  its  manner  of  action  crystallized 
instantly  in  my  mind,  along  the  lines  of  force,  so  to  speak,  of  the 
Proteomorphic  theory.  At  once  it  seemed  clear  to  me  that  we 
had  to  do  with  a  protein  response;  that  the  cohorts  of  leuco- 
cytes and  red  corpuscles  were  stimulated  into  being  and  into 
renewed  activities  to  meet  a  protein  invasion ;  and  that  the  ob- 
served action  on  the  cancer  cells  was  only  an  incidental  effect 
due  to  the  fact  that  these  cells  are  themselves  foreign  proteins 
and,  therefore,  fall  within  the  range  of  activities  of  the  cor- 
puscles. The  preliminary  blood  studies  that  were  already  under 
way,  the  full  details  of  which  will  be  given  presently,  appeared 
to  justify  the  inference.  The  observed  facts  linked  with  the 
Proteomorphic  theory,  in  my  mind  at  any  rate,  in  a  way  abso- 
lutely convincing. 

Immediately,  and  at  a  single  sitting,  I  wrote  the  paper  explain- 
ing the  action  of  the  remedy  in  the  light  of  the  Proteomorphic 
Theory,  which  was  published  in  the  New  York  Medical  Journal 
of  October  2,  1915. 

I  weigh  my  words  very  carefully,  yet  I  speak  entirely  with- 
out hesitation,  when  I  express  the  conviction  that  a  new  era 
in  therapeutics  was  foreshadowed  in  that  publication. 

In  speaking  thus,  I  do  not  mean  to  refer  in  particular  to  the 
treatment  of  cancer.  That,  as  I  clearly  conceived  at  the  time, 
is  only  an  incident.  The  subject  involved  is  much  larger.  I 
stated  this  explicitly  in  the  article  in  question,  enunciating  the 
opinion  that  a  principle  of  protein  response  had  been  (quite  by 
accident)  invoked  that  would  apply  against  all  protein  infections. 
I  expressly  stated  the  opinion  that,  in  the  attempt  to  explain  the 
rationale  of  the  action  through  which  the  vegetable  proteins  bring 
about  a  beneficent  increase  in  the  armies  of  leucocytes  and  ery- 
throcites,  we  "gain  glimpses  of  an  entirely  new  field  of  thera- 
peutics and  shall  be  enabled  to  give  at  least  a  proximal  explana- 


114      THE   PROTEOMORPHIC  THEORY   AND  THE    NEW    MEDICINE 

tion  of  the  exact  manner  of  action  of  a  remedy,  the  introduction 
of  which,  I  believe,  constitutes  the  inauguration  of  a  method 
that  must  in  future  rank  with  serum  therapy  and  vaccine  therapy 
— if,  indeed,  it  does  not  altogether  outstrip  or  totally  supplant 
both  these  relatively  new  additions  to  the  equipment  of  the  prac- 
tical physician." 

Such  a  view  as  this,  if  presented  without  both  theoretical  and 
clinical  backing,  must  have  seemed  heretical.  It  carried  the 
clear  implication  that  a  non-specific  protein  might  serve  as  an 
antigen  capable  of  decompounding  proteins  of  many  types,  in- 
cluding the  bodies  of  various  pathogenic  bacteria  and  various 
types  of  "malignant"  cells. 

The  suggestion  ran  counter  to  the  dominant  medical  thought 
of  the  moment.  The  familiar  facts  regarding  diphtheria  anti- 
toxin, Wright's  anti-typhoid  vaccine  and  allied  vaccines,  and 
Ehrlich's  salvarsan  (to  mention  typical  examples  of  three  new 
types  of  medication)  had  revived  in  the  mind  of  the  profession 
the  old  hope  that  specific  medication  was  to  give  final  answer 
to  all  therapeutic  problems.  In  the  cancer  field,  as  well  as  in 
the  field  of  bacteriology,  recent  effort  had  nearly  all  been  directed 
along  the  lines  either  of  specific  antigens  or  of  remedies  having 
elective  affinity  for  particular  cells.  Various  attempts  to  develop 
a  cancer  anti-serum ;  Vaughan's  use  of  residual  products  of  the 
cancer  cell,  and  Hodenpyl's  use  of  ascitic  fluid  of  a  cancer  sub- 
ject were  typical  illustrations  of  one  method;  and  the  colloidal 
copper  treatment  of  Leo  Loeb  and  selenium  experiments  of  Ehr- 
lich  and  Wassermann  were  illustrations  of  others. 

It  may  fairly  be  said  that  most  workers  in  the  field  were  so 
thoroughly  imbued  with  the  idea  of  specific  therapy  as  to  cause 
them  to  look  askance  at  any  suggestion  of  a  more  general 
method. 

Perhaps  I  cannot  better  illustrate  this  than  by  stating  that 
among  the  medical  men  who  were  most  closely  concerned  with 
the  introduction  of  the  vegetable  extract  treatment,  there  were 
those  who  were  inclined  to  believe  that  the  extract  would  be 
found  to  contain  something  having  a  selective  affinity  for  can- 
cer cells,  and  hence  falling  within  the  scope  of  specific  medica- 
tion. The  thought  of  a  magical  "vitamine"  was  at  least  vaguely 
in  their  minds.  Like  the  users  of  Dr.  Gwyer's  "X-substance," 
which  produced  analogous  results,  they  were  mystified  by  the 
seeming  complexity  of  the  agent  empirically  used.  These  men 
looked  with  frank  scepticism  on  the  theoretical  interpretation 
of  the  action  of  the  remedy  that  I  presented  in  the  paper  of 
October  2,  1915,  and  did  not  for  some  time  thereafter  accept 
the  view  that  a  general  principle  of  protein  antagonism  had  been 
evoked. 


DISCOVERY   OF   PROTEIN    PRINCIPLE   IN   THERAPEUTICS        115 

It  is  fair  to  add  that  I  myself  was  not  prepared  to  demon- 
strate at  the  time  when  this  paper  was  published  that  there  might 
not  be  other  agents,  for  example,  chlorophyll,  in  the  extract  that 
had  a  share  in  the  therapeutic  action.  The  demonstration  that 
the  protein  alone  was  the  effective  agent  was  the  work  of  later 
months,  to  be  narrated  in  a  moment.  But  the  discovery  of  the 
protein  principle,  and  the  interpretation  of  its  action  in  the  light 
of  the  Proteomorphic  theory,  was  clearly  revealed  in  this  paper 
of  October  2,  1915.  My  subsequent  work  was  to  elaborate  and 
demonstrate  the  principle,  but  in  no  wise  to  change  its  essen- 
tials as  presented  at  this  time.  There  is  reason  to  believe  that 
the  paper  found  a  responsive  audience — witness  the  work  in 
non-specific  protein  therapy  that  a  few  months  later  began  to 
attract  attention  in  the  medical  journals. 

Meantime  I  had  made  a  statistical  study  of  the  results  of  the 
use  of  the  vegetable  extract  in  the  treatment  of  cases  of  inop- 
erable cancer — the  only  cases  to  which  it  was  at  first  applied. 
The  article  in  which  I  summarized  the  result  of  this  study  ap- 
peared in  the  New  York  Medical  Journal  of  November  13,  1915. 
A  summary  of  the  results  will  be  presented  elsewhere.  For  the 
moment  our  chief  concern  is  with  the  theoretical  aspects  of 
the  subject  rather  than  with  the  clinical  details.  Suffice  it  that 
the  clinical  experience,  statistically  summarized,  overwhelmingly 
sustained  the  belief  that  the  bodily  response,  whether  or  not  of 
corpuscular  origin,  was  of  a  nature  to  antagonize  the  cancer 
cells,  and  favorably  to  influence  the  general  conditions  of  the 
patient,  as  evidenced  by  decrease  or  cessation  of  pain  in  a  large 
proportion  of  cases ;  modification  or  annulment  of  malodor ;  im- 
proved appetite,  sleep,  and  sense  of  well  being;  and,  in  a  sur- 
prisingly large  percentage  of  cases,  actual  regression  of  the  can- 
cer mass  itself. 

All  these  clinical  changes  found  explanation,  according  to  my 
belief,  in  the  modified  numbers  and  enhanced  enzymic  activ- 
ities of  the  blood  corpuscles,  along  the  lines  of  the  Proteomor- 
phic Theory.  This  opinion  found  support  in  the  elaborate  studies 
of  the  corpuscles,  in  the  counting  chamber  and  on  the  smear, 
which  were  carried  out  by  me  personally,  or  under  my  direct 
supervision,  in  the  ensuing  months. 

These  studies  of  the  blood  were  undertaken  without  prejudice 
or  preconception.  The  earlier  counts,  numerical  and  differential, 
were  made  under  my  direction,  to  be  sure,  but  by  an  assistant 
who  had  scant  knowledge,  or  perhaps  no  knowledge  at  all,  of 
the  Proteomorphic  Theory,  and  who  made  and  recorded  obser- 
vations automatically,  without  attempting  to  classify  or  sum- 
marize them  or  to  draw  conclusions.  When  these  observations 
were  tabulated  by  me,  they  at  once  revealed  unequivocally  cer- 


116      THE   PROTEOMORPHIC  THEORY   AND  THE   NEW    MEDICINE 

tain  characteristic  and  very  conspicuous  modifications  of  the 
blood,  comprising,  in  brief  summary,  increase  of  haemoglobin, 
increase  of  the  number  of  red  corpuscles,  and  striking  modi- 
fication of  the  differential  leucocyte  count,  in  the  direction  of 
lessening  the  relative  number  of  polynuclears,  and  markedly  in- 
creasing the  mononuclears,  and  in  particular  the  large  monocytes. 
The  last-named  feature  appeared  to  link  suggestively  with 
Vaughan's  observations  on  the  enzymic  activities  of  the  large 
mononuclears  in  connection  with  cancer  cells. 

Elaborate  analyses  of  the  blood  count,  and  of  subsequent 
studies  along  these  lines,  are  made  in  later  sections  of  the  pres- 
ent work.  Here  it  suffices  to  call  attention  to  the  fact  that  these 
studies  from  the  outset  confirmed  in  my  mind  the  probability 
that  we  had  to  do  with  a  protein  response,  and  that  the  Prote- 
omorphic  Theory  supplied  a  key  to  the  interpretation  of  the 
observed  phenomena. 

The  clinical  results  hitherto  observed  were  not  very  different 
from  those  that  had  been  attained  by  various  workers  with 
different  types  of  animal  extracts,  sera,  and  vaccines  (Fichera's 
autolysate,  Hodenpyl's  ascitic  fluid,  Gwyer's  X-substance,  Coley's 
fluid),  except  that  they  were  carried  out  on  a  more  elaborate 
scale ;  but  the  studies  of  the  blood  in  this  connection  were  alto- 
gether new,  and  they  constituted  the  determining  factor  in  con- 
firming in  my  mind  the  belief  that  the  new  therapeutic  principle 
which  I  conceived  to  underlie  the  observed  phenomena  might 
carry  us  far. 

It  seemed  to  me  imperative,  therefore,  that  I  should  put  aside 
other  work  and  devote  my  time  to  the  interpretation  of  this 
principle,  which  appeared  to  adumbrate  vast  therapeutic  possi- 
bilities. 

I  was  more  urgently  impelled  to  do  so  because,  with  enlarged 
experience,  it  became  increasingly  evident  that  the  glowing  an- 
ticipations of  some  of  the  earlier  users  of  the  vegetable  extract 
in  the  treatment  of  cancer  had  led  to  bitter  disappointment,  in 
that  patients  who  seemed  at  first  to  be  on  the  highway  to  re- 
covery reached  a  static  period  presently  and  then  relapsed  and 
gradually  passed  down  the  characteristic  decline  to  the  usual 
fatal  termination. 

I  heard  over  and  over  the  same  story,  from  scores  of  med- 
ical correspondents.  At  first  the  improvement  of  the  patient  had 
been  almost  miraculous.  High  hopes  were  entertained  of  a 
recovery,  although  previously  the  case  had  been  regarded  as 
absolutely  hopeless.  But  now  progress  was  no  longer  cumula- 
tive; the  patient  perhaps  remained  more  comfortable,  with  less 
pain,  less  of  malodor,  but  there  was  a  general  physical  decline; 
the  tumor's  course  was  no  longer  checked,  the  symptoms  of 


DISCOVERY   OF  PROTEIN   PRINCIPLE   IN   THERAPEUTICS        117 

cachexia  were  progressive,  and  the  end  was  obviously  at  hand. 
The  life  of  the  patient  had  undoubtedly  been  made  more  comfort- 
able, and  had  almost  certainly  been  prolonged;  but  the  ultimate 
result  had  not  been  what  the  friends  of  the  patient  had  hoped 
for,  and  what  the  physician  had  for  a  time  allowed  himself  to 
expect. 

There  were  exceptions  to  this,  it  is  true.  A  few  cases  out  of 
the  hundreds  appeared  to  have  gone  to  a  clinical  recovery  that 
seemed  to  give  promise  of  permanency.  But  these  exceptions, 
notable  in  themselves,  were  few  and  far  between. 

This,  of  course,  was  precisely  the  history  of  the  various  ante- 
cedent biological  measures  in  the  treatment  of  cancer — the  experi- 
ence that  had  led  to  the  abandonment  of  most  of  these  methods 
after  a  brief  term  of  use.  But  to  me  the  experience  seemed 
neither  unexpected  nor  disheartening.  I  had  been  careful  to 
point  out  in  my  statistical  reports  that  these  were  only  prelim- 
inary and  that  the  final  story  could  not  be  told  for  months  to 
come.  I  had  pointed  out  that  what  was  being  sought  was  a 
scientific  medicament  and  not  a  magician's  wand.  I  had  repu- 
diated from  the  outset  the  suggestion  that  the  particular  vege- 
table extract  in  question  had  any  specific  qualities  whatsoever 
that  set  it  aside  from  any  other  extract  containing  non-toxic 
proteins. 

And  what  was  still  more  important — as  the  sequel  will  show — 
I  had  conceived  the  idea  that,  if  the  active  agent  involved  was 
indeed,  as  I  believed,  a  protein,  as  such,  there  could  be  nothing 
more  natural  than  the  gradual  immunization  of  the  system  against 
the  particular  proteins  employed,  with  the  result  that  the  cor- 
puscular response  would  presently  cease  to  be  cumulative.  This, 
as  it  seems  to  me,  would  account  for  the  observed  fact  that  the 
patient  who  had  at  first  shown  extraordinary  response  presently 
reached  a  static  condition,  and  then  entered  on  a  period  of 
decline. 

The  fact  that  the  use  of  excessive  dosage,  or  the  accidental 
or  intentional  injection  of  the  extract  into  a  vein,  with  a  re- 
sultant anaphylactic  shock,  had  been  observed  sometimes  to  bring 
about  a  new  period  of  favorable  progress  in  a  case  that  had 
reached  this  static  phase,  appeared  to  me  to  confirm  the  view 
just  presented. 

The  essential  fact,  as  I  conceived  it,  now  established  irre- 
futably, was  that  the  parenteral  introduction  of  a  protein  could 
bring  about  a  response  that  would  produce  such  clinical  modi- 
fications. The  fact  that  the  response  was  not  indefinitely  per- 
sistent, and  that  the  ultimate  clinical  results  fell  short  of  the 
miraculous,  seemed  to  me  a  detail.  A  very  tragic  detail,  to  be 
sure,  for  the  individual  patient ;  but  by  no  means  condemnatory 


118      THE   PROTEOMORPHIC  THEORY   AND  THE    NEW    MEDICINE 

of  the  procedure  as  a  whole,  and  assuredly  not  precluding  the 
possibility  of  further  development  along  similar  lines. 

Therefore  I  re-entered  the  laboratory  (several  years  of  my  ear- 
lier professional  life  had  been  devoted  to  chemistry  and  pathology) 
and  took  up  once  more  the  routine  of  office  practice,  and  the  labo- 
rious but  ever  fascinating  grind  with  test  tube  and  microscope.  The 
dominant  thought  was  to  test  the  protein  principle  as  interpreted 
in  terms  of  the  Proteomorphic  Theory.  My  published  contention 
that  we  had  to  do  with  no  specific  agent,  but  with  a  general 
principle  that  could  be  utilized  in  all  kinds  of  protein  infec- 
tions had  found  a  measure  of  practical  support  in  the  success- 
ful treatment  of  a  few  cases  of  rheumatoid  arthritis  and  one 
almost  spectacular  case  of  tuberculosis.  The  modification  of  the 
blood  in  these  cases  had  been  characteristic;  and  similar  modi- 
fications were  observed  in  patients  treated  with  sheep  serum. 

My  belief  that  the  observed  modifications  are  of  the  nature 
of  a  response  to  the  introduction  of  a  foreign  protein,  and  not 
to  any  particular  protein,  had  become  a  firm  conviction.  But 
it  required  further  experimental  support. 

An  obvious  way  to  test  the  matter  would  be  to  produce  pro- 
tein extracts  from  a  variety  of  non-toxic  vegetable  substances, 
and  to  observe  their  effects  when  used  hypodermically.  Such 
extracts  were  made  from  alfalfa  seed,  millet  seed,  rape  seed, 
hemp  seed  (and  subsequently  from  numerous  other  sources), 
carefully  standardized  by  a  nitrogen  determination,  and  clin- 
ically tested  with  a  variety  of  patients,  most  of  whom  had  long 
been  under  treatment  with  the  original  protein  extract,  but  some 
of  whom  had  never  previously  been  treated  with  proteins  of 
any  kind. 

The  vegetable  proteins  thus  used  were  at  first  prepared  by 
macerating  the  ground  seeds  in  either  salt  solution  or  solu- 
tion of  sodium  hydroxide.  A  concentration  varying  from  two 
to  four  milligrams  of  nitrogen  to  the  cubic  centimeter  was  af- 
fected by  the  Kjeldahl  method,  and  ultimately  a  standardization 
on  the  basis  of  three  milligrams  of  nitrogen,  or  approximately 
a  two  per  cent,  protein  solution,  was  adopted  as  a  satisfactory 
and  convenient  compromise.  Sometimes  the  proteins  were  used 
in  the  original  solution ;  in  other  cases  the  protein  was  precipi- 
tated from  the  extract  with  acetic  or  hydrochloric  acid ;  washed, 
and  redissolved  in  a  solution  of  sodium  hydroxide.  In  any 
event,  the  extract  was  always  made  slightly  alkaline  with  sodium 
hydroxide,  the  slightest  degree  of  acidity  rendering  it  painful 
on  administration.  I  had  early  discovered  that  this  was  one 
source  of  irritation  that  made  the  administration  of  the  original 
extract  unpleasant. 

Extracts  thus  prepared  were  first  employed  therapeutically  in 


DISCOVERY   OF   PROTEIN    PRINCIPLE   IN    THERAPEUTICS        119 

July,  1916.  They  were  tested  side  by  side  with  extracts  made 
from  the  conglomerate  group  of  herbs  originally  employed,  or 
from  this  powder  with  part  of  the  original  constituents  elim- 
inated. Comparative  tests  were  continued  for  a  period  of  six 
months,  after  which  the  original  extract  was  entirely  aban- 
doned, the  uncomplicated  protein  solutions  made  from  alfalfa  seed, 
alfalfa  meal,  rape  seed,  millet  seed,  hemp  seed,  and  from  egg 
albumin  and  milk  albumin,  used  singly  or  in  combination,  hav- 
ing been  demonstrated  to  produce  the  same  clinical  and  blood 
responses,  and  bearing  about  the  same  relation  to  the  original 
clumsy  formula  that  a  modern  preparation  of  digitalis  bears 
to  the  shot  gun  formula  of  the  old  woman  who  first  used  an 
infusion  of  foxglove  combined  with  sundry  inert  herbs. 

In  a  word,  the  validity  of  my  early  contention  that  .the  re- 
sponse was  essentially  a  protein  response  was  abundantly  demon- 
strated. 

Moreover,  my  expectation  that  a  new  protein  would  produce 
a  new  response,  thus  supplying  means  to  overcome  the  stasis 
accompanying  immunization  to  the  first  protein  employed,  was 
also  justified  in  the  most  gratifying  manner.  Cases  that  had 
become  static  after  having  undergone  an  original  period  of  prog- 
ress, took  on  a  new  period  of  favorable  progress  on  the  admin- 
istration of  the  new  proteins.  The  very  first  patient  to  whom 
alfalfa  protein  was  administered  showed  the  influence  of  the 
new  protein  in  a  very  striking  way.  This  was  a  case  of  meta- 
static  recurrence  after  excision  of  the  cancer  of  the  breast. 
The  neoplasm  had  regressed  under  early  treatment,  but  had 
become  static,  with  a  seeming  tendency  to  take  on  new  growth. 
It  at  once  regressed  when  the  alfalfa  protein  was  administered, 
and  presently  nothing  remained  but  a  pea-sized  nodule  just  under 
the  skin,  which  was  excised  with  local  anesthesia.  The  patient 
went  on  to  seemingly  complete  recovery,  and  at  the  present 
writing,  eighteen  months  after  the  disappearance  of  all  symp- 
toms or  appearances  of  abnormality,  she  is  in  robust  condition 
and  seemingly  in  complete  health. 

THEORY  TESTED  BY  PROPHECY 

It  has  been  said  that  the  final  test  of  the  truth  of  a  theory  is 
that  its  application  shall  enable  one  to  prophesy.  It  is  with 
peculiar  satisfaction,  then,  that  I  make  this  succinct  record  of 
prophecies  fulfilled.  Given  a  therapeutic  agent  extracted  by  an 
unknown  process  from  a  conglomerate  mixture  of  drugs,  and 
showing  clinical  response  altogether  inexplicable  by  any  known 
principle  of  therapeutics ;  I  predicated  the  response — guided  by 
the  Proteomorphic  Theory — as  due  to  no  ordinary  pharmaceu- 


120      THE   PROTEOMORPHIC   THEORY  AND  THE    NEW    MEDICINE 

tical  property  of  any  of  the  ingredients,  but  as  a  general  response 
to  the  proteins  that  chanced  to  be  extracted  along  with  sundry 
inert  constituents ;  and — still  guided  by  the  Proteomorphic 
Theory — I  went  on  to  predict  that  it  would  be  possible  to  make 
numberless  extracts  having  precisely  comparable  therapeutic  ac- 
tion from  altogether  unrelated  vegetable  products — that,  in  short, 
any  non-toxic  protein  would  suffice,  in  a  measure  at  any  rate, 
to  take  the  place  of  the  proteins  under  observation.  I  predicted 
that  it  would  be  possible  to  stimulate  a  new  response  by  intro- 
ducing a  new  protein  after  the  system  had  become  immunized  to 
an  earlier  one.  I  further  suggested  that  quantitative  differences 
would  be  found  in  the  response  to  different  proteins,  in  accord- 
ance with  the  nearness  or  remoteness  of  the  individual  protein, 
botanically  speaking,  to  the  proteins  of  ordinary  foodstuffs. 

All  of  these  prophecies  have  been  abundantly  substantiated 
by  experiences  that  now  extend  over  a  period  of  nearly  twenty 
months,  fortified  by  my  personal  observation  of  more  than  one 
hundred  carefully  studied  cases  in  which  clinical  manifestations 
were  constantly  checked  by  blood  examinations ;  and  corrob- 
orated by  the  experience  of  a  body  of  representative  physicians 
in  all  parts  of  the  United  States. 

Under  date  of  December  1,  1916,  I  issued  a  Monograph  of 
126  pages  bearing  the  title  The  Proteal  Treatment  of  Cancer  and 
Allied  Conditions;  A  Practical  Study  of  a  New  Therapeutic 
Principle  as  Interpreted  in  the  Light  of  the  Proteomorphic 
Theory.  A  portion  of  the  contents  of  this  Monograph  is  in- 
corporated in  the  text  of  the  present  book  and  may  there  be  con- 
sulted in  detail.  Here  I  wish  to  quote  from  the  Foreword  a 
few  sentences  that  will  suggest  the  confidence  which  enlarged 
experience  had  inspired — confidence  which  the  yet  wider  experi- 
ence of  another  fifteen  months  has  abundantly  fortified.  On 
December  1,  1916,  then,  I  felt  justified  in  making  the  following 
emphatic  estimate  of  results  attained;  which  now,  fifteen  months 
later,  I  reiterate  with  no  less  emphasis : 

"That  proteals,  properly  administered,  assuage  the  pain  of 
the  cancer  sufferer  in  a  large  proportion  of  cases;  neutralize 
malodor;  stimulate  the  blood  count  and  with  it  the  manifesta- 
tions of  improved  health  and  comfort ;  and  in  a  conspicuous  pro- 
portion of  cases  cause  unmistakable  modifications  in  the  condi- 
tion of  the  neoplasm  itself,  amounting  frequently  to  marked 
regression — is  scarcely  more  open  to-day  to  dispute  than  that 
digitalis  stabilizes  the  heart  beat,  that  quinine  antagonizes  the 
plasmodium  of  malaria,  or  that  mercury  combats  the  germ  of 
syphilis. 

"There  remains,  however,  a  question  as  to  the  amount  of  ben- 
efit that  may  be  expected  in  any  individual  case;  and  the  all- 


DISCOVERY   OF   PROTEIN    PRINCIPLE   IN   THERAPEUTICS        121 

important  question  as  to  whether  seeming  recoveries  under  the 
proteal  treatment  are  complete  and  permanent  recoveries.  These 
questions  will  be  discussed  in  the  ensuing  pages,  but  with  no 
suggestion  that  a  final  answer  as  to  the  permanency  of  seeming 
cures  can  be  made  except  after  the  lapse  of  a  long  period  of  time. 

"But  if  the  question  of  the  possible  cure  of  cancer  by  the 
new  type  of  medication  must  be  left  in  abeyance,  there  is  no 
occasion  for  delay  in  spreading  broadcast  the  knowledge  that 
the  proteals  bring  a  message  of  new  hope  for  the  cancer  sufferer, 
whatever  the  form  or  stage  of  progress  of  his  malady.  The 
proteal  remedies  have  already  conferred  unique  benefits  upon 
not  far  from  3,000  sufferers ;  they  have  been  responsible  for 
an  enormous  alleviation  of  pain  in  the  aggregate,  and  for  a 
notable  extension  of  human  lives. 

"According  to  recent  statistics,  cancer  accounts  for  five  or 
six  per  cent,  of  all  deaths.  That  is  equivalent  to  saying  that 
at  least  five  million  people  are  living  in  the  United  States  to-day 
who  must  die  of  cancer  unless  medical  science  in  the  coming 
years  deals  more  effectively  with  the  malady  than  it  has  known 
how  to  do  in  the  past. 

"I  dare  to  hope  that  the  facts  cited  in  this  monograph  justify 
the  belief  that  we  are  beginning  to  see  a  little  light  in  this  dark 
field. 

"I  dare  even  to  hope  that  the  beginning  of  the  end  of  the  can- 
cer scourge  is  at  hand.  Proteal  treatment  may  not  offer  the 
final  solution  of  the  cancer  problem ;  but  I  verily  believe  that 
it  points  the  way  to  a  solution. 

"In  any  event,  the  proteal  treatment  offers  to-day  a  hitherto 
unattainable  measure  of  solace,  and  a  message  of  new  hope  for 
cancer  sufferers  everywhere  in  the  world." 

To  be  able  to  write  such  an  estimate,  secure  in  the  belief  that 
the  evidence  already  in  hand  abundantly  justified  it,  might  well 
be  considered  adequate  reward  for  two  years  of  strenuous  and 
nerve-racking  investigation.  But  in  point  of  fact  this  was  only 
the  beginning,  as  I  then  conceived  it,  and  as  I  now  conceive  it. 
In  the  article  of  October  2,  1915,  in  the  New  York  Medical 
Journal  I  had  expressly  repudiated  the  idea  that  the  protein 
response  has  any  specific  relation  to  cancer  except  in  so  far  as 
the  cancer  mass  chances  to  be  composed  of  protein  matter,  as- 
serting the  belief  that  the  province  of  protein  therapy  is  the 
entire  .field  of  protein  infection.  I  purposely  refrained  from 
mentioning  bacterial  infections  as  such,  for  I  knew  that  at  best 
the  suggestion  of  so  general  a  principle  as  that  implied  would 
tax  the  credulity  of  the  profession.  But  that  I  had  the  bac- 
terial infections  in  mind  is  implied  in  the  fact  that  these  are, 
as  a  matter  of  course,  protein  infections;  and  is  explicitly  sug- 


122      THE   PROTEOMORPHIC   THEORY   AND  THE    NEW    MEDICINE 

gested  in  the  prediction  above  quoted  that  the  non-specific  pro- 
tein method  "must  in  future  rank  with  serum  therapy  and  vaccine 
therapy — if,  indeed,  it  does  not  altogether  outstrip  or  totally 
supplant  both  these  relatively  new  additions  to  the  equipment  of 
the  practical  physician." 

The  confidence  that  underlay  this  prediction  had  led  me  to 
urge  the  use  of  the  non-specific  protein  extracts  in  all  manner 
of  toxaemias;  and,  as  rapidly  as  opportunity  offered,  the  matter 
was  put  to  practical  tests,  in  my  own  practice,  and  through  co- 
operation with  several  hundred  progressive  physicians  to  whom 
proteals  were  supplied  from  my  experimental  laboratory.  As  a 
result,  it  has  been  demonstrated,  within  two  years  of  the  time 
when  the  prophecy  was  made,  that  intestinal  toxaemias,  anaemias, 
neurasthenias,  rheumatoid  conditions  (including  rheumatoid  ar- 
thritis), tuberculosis,  asthma,  and  psoriasis  fall  within  the  scope 
of  the  protein  response  no  less  than  cancer,  and  there  is  no  rea- 
son to  suppose  that  even  this  comprehensive  list  of  maladies 
exhausts  the  possibilities  of  the  method. 

OTHER  REMEDIAL  USES  OF  THE  PROTEALS 

The  Monograph,  though  dealing  primarily  with  cancer,  made 
explicit  reference  to  these  wider  and,  in  the  aggregate,  more 
important  applications  of  Proteal  Therapy,  in  part  as  follows : 

It  remains  to  give  brief  consideration  to  sundry  conditions  of 
the  organism  not  characterized  by  the  presence  of  malignant 
neoplasms,  but  associated  with  organic  maladjustments  that  make 
possible  the  development  of  such  neoplasms;  and  directly  char- 
acterized by  proliferation  of  protoplasmic  tissues  in  my  judg- 
ment comparable  with  cancer  proper — though  not  commonly 
viewed  in  this  light  by  physiologists  or  pathologists. 

I  have  in  mind  various  conditions  characterized  by  disturb- 
ances of  nutrition  and  assimilation  that  lead  to  abnormal  growth 
of  cells  in  one  region  or  another  of  the  body,  all  evidencing 
conditions  of  hyperplasia  that  had  certain  elements  of  "malig- 
nancy," inasmuch  as  they  are  deleterious  to  the  organism,  though 
varying  enormously  in  the  degree  of  their  obnoxiousness. 
Among  these  conditions  are :  ( 1 )  Anaemic  obesity,  in  which  law- 
less adipose  cells  encroach  on  more  useful  tissues;  (2)  pernicious 
anaemia  and  the  lymphaemias  and  myelaemias,  characterized  by 
hyperplasia  of  the  blood-forming  tissues;  (3)  glandular  hyper- 
trophy, as  in  goiter,  thymus  enlargement,  and  splenomegaly ;  (4) 
rheumatoid  arthritis,  characterized  by  hyperplasia  of  tissues  as- 
sociated with  joints;  (5)  general  arteriosclerosis,  characterized 
by  hyperplasia  of  the  tissues  of  the  arterial  walls ;  (6)  sundry 


DISCOVERY   OF   PROTEIN    PRINCIPLE   IN   THERAPEUTICS        123 

lipomas  and  fibromas  of  "benign"  character;  in  addition  to  (7) 
the  neoplasms  commonly  recognized  as  "malignant." 

I  venture  to  associate  all  these  conditions,  and  to  trace  them 
to  a  common  origin  in  maladjustments  of  protein  metabolism, 
and  I  suggest  that  it  might  not  be  illogical  to  group  them  all 
under  some  such  generic  title  as  hyperproteomorphism,  or  the 
cancerous  condition.  I  shall  not  attempt  here  to  discuss  even 
in  briefest  detail  the  interesting  questions  in  pathology  that  arise 
in  connection  with  the  implied  association  of  conditions  of  such 
seeming  diversity.  Such  a  discussion  will  form  the  basis  of 
another  book.  Here  I  wish  to  point  out  very  briefly  two  or 
three  sets  of  clinical  facts  that  give  at  least  a  measure  of  sup- 
port to  the  unorthodox  conception  applied  in  this  classification. 

I  would  first  call  attention  to  the  familiar  fact  that  a  well- 
known  type  of  fatty  and  mucinous  hypertrophy  known  as  myx- 
oedema  is  associated  with  perversions  of  the  thyroid  function; 
and  the  further  fact  that  there  is  believed  to  be  a  close  asso- 
ciation between  the  integrity  of  the  hormone  functioning  and 
bodily  metabolism  in  general. 

Without  attempting  to  point  out  except  in  this  general  way 
what  I  conceive  to  be  the  bearing  of  the  observation,  I  wish  to 
note  that  it  has  been  observed  by  at  least  one  physician  who 
was  administering  the  mixed  proteals  in  a  case  of  cancer  that 
an  enlarged  thyroid  disappeared  during  the  treatment. 

Observations  along  this  line  have  not  yet  reached  the  point  of 
readiness  for  detailed  publication.  By  way  of  anticipation,  how- 
ever, we  may  note  that  the  modification  of  blood  count  under 
influence  of  the  thyroid  serum  is  singularly  like  that  brought 
about  by  the  proteals ;  suggesting  that  the  action  of  the  serum 
is  partly  explicable  on  the  basis  of  its  protein  content.  Doubt- 
less there  is  also  an  anti-thyroid  enzyme  element,  but  the  agent 
that  causes  decrease  in  size  of  the  enlarged  thyroid  is  probably 
not  this  anti-ferment,  but  the  sheep-serum  protein. 

In  the  next  instance  I  would  note  that  in  a  case  of  cancer 
under  mixed  vegetable  protein  treatment  there  existed  the  com- 
plication of  severe  rheumatoid  arthritis.  The  latter  condition 
cleared  up  entirely — a  seeming  cure  being  effected  under  the 
protein  treatment.  This  observation  led  to  the  administration 
of  the  proteals  in  several  cases  of  rheumatoid  arthritis  uncom- 
plicated by  the  presence  of  cancer ;  and  the  results  of  such  treat- 
ment have  been  highly  gratifying.  In  a  recent  case  the  response 
to  rape  seed  protein  by  itself  seemed  as  active  as  the  response 
to  the  combined  proteins. 

As  regards  the  relation  of  the  new  treatment  to  the  form  of 
nutritional  maladjustment  manifesting  itself  in  pernicious  anae- 


124      THE   PROTEOMORPHIC  THEORY  AND  THE   NEW   MEDICINE 

mia,  I  cannot  do  better  than  to  quote  a  letter  received  not  long 
ago  from  a  physician  in  Michigan,  which  is  self-explanatory. 

"I  have  been  using  vegetable  proteins  in  a  late  stage  of  per- 
nicious ansemia  on  purely  theoretical  grounds.  After  ten  injec- 
tions have  found  an  increase  of  over  15  per  cent,  in  the  red 
cells  with  an  accompanying  favorable  alteration  in  the  differential 
leucocyte  count,  and  have  noted  nucleated  red  cells  for  the  first 
time  since  the  treatment  was  begun. 

"The  patient,  a  man  over  50  years  of  age,  carpenter  by  trade, 
is  without  means,  having  been  unable  to  work  for  over  18 
months.  I  ordered  the  remedy  for  him  on  my  own  responsi- 
bility, having  become  familiar  with  the  product  through  using 
it  in  a  supposedly  hopeless  case  of  carcinoma  of  the  liver,  sec- 
ondary to  gall  bladder  carcinoma  in  my  wife's  mother.  Gall 
bladder  and  neighboring  involved  liver  were  removed  and  re- 
ported by  pathologist  at  University  of  Michigan  as  carcinoma, 
and  a  hopeless  prognosis  given." 

Vegetable  protein  treatment  was  undertaken,  and  continued 
between  three  and  four  months ;  after  which,  according  to  the 
report : 

"The  patient  is  in  better  flesh  than  ever  before,  is  well  and 
comfortable  in  every  way,  and  the  right  lobe  of  liver,  which  is 
low,  feels  perfectly  smooth  and  healthy." 

It  will  be  observed  that  this  letter  has  double  interest,  inas- 
much as  it  bears  on  the  question  of  the  value  of  combined  pro- 
teins in  the  treatment  of  a  "supposedly  hopeless  case  of  carci- 
noma of  the  liver,"  as  well  as  on  the  question  of  its  value  in  the 
treatment  of  pernicious  anaemia.  It  is,  however,  only  the  lat- 
ter point  that  is  at  the  moment  pertinent.  I  shall  not  elaborate 
the  point,  however,  beyond  stating  that  a  letter  from  the  same 
physician  received  several  weeks  later  confirms  the  observation 
that  the  condition  of  this  patient  is  benefited  by  the  treatment. 
Obviously  this  is  no  more  than  might  be  expected  of  the  admin- 
istration of  a  remedy  which  has  been  observed  in  a  very  large 
number  of  cases  to  produce  striking  and  beneficial  modifications 
of  the  blood  count. 

A  further  report  on  the  progress  of  this  case  comes  to  hand 
in  a  still  more  recent  letter  bearing  date  of  October  19,  1916, 
telling  of  the  resumption  of  the  treatment  after  a  considerable 
intermission. 

"The  pernicious  anaemia  case  has  shown  a  remarkable  change 
for  the  better  since  using  last  package  of  ampules.  This  patient, 
a  county  case,  was  in  a  somnolent  condition,  and  in  fact  had  been 
removed  from  ward  to  private  room  to  die.  He  is  now  bright, 
has  lost  all  the  general  cedema,  eats  well,  and  wishes  to  be  up 
and  around." 


DISCOVERY    OF    PROTEIN    PRINCIPLE    IN    THERAPEUTICS         125 

Just  as  the  physician  above  quoted  was  led  "on  theoretical 
grounds,"  following  his  observations  of  the  results  of  the  pro- 
teal  treatment,  to  inquire  whether  the  remedy  might  not  be  of 
value  in  connection  with  pernicious  anaemia,  other  physicians  have 
questioned  whether  its  capacity  to  stimulate  the  production  of 
corpuscular  enzymes  and  to  bring  up  the  blood  count  might  not 
make  it  of  value  in  the  treatment  of  bacterial  diseases. 

Very  brief  but  specific  reference  to  such  a  possibility  was, 
indeed,  made  in  my  paper  of  October  2nd,  in  the  New  York 
Medical  Journal.  In  referring  to  this  in  the  Monograph  of 
December  1,  1916,  the  suggestive  comment  was  made  that: 
"A  limited  experience  in  the  treatment  of  tuberculosis  appears 
to  warrant  the  hope  that  non-toxic  vegetable  proteins  will  prove 
available  to  fortify  the  defensive  mechanism  of  the  body  (ac- 
cording to  the  present  thesis)  by  stimulating  the  corpuscular 
activities  against  the  tubercle  bacillus.  If  a  non-specific  protein 
can  produce  this  effect,  there  would  seem  to  be  no  reason  why 
the  same  protein,  or  allied  proteins,  may  not  give  effective  aid 
in  combating  all  types  of  pathogenic  bacteria." 

The  above,  it  will  be  observed,  is  in  effect  a  summary  of  the 
stage  of  development  of  Proteal  Therapy  in  its  wider  applications, 
toward  the  close  of  the  year  1916. 

The  year  1917,  following  the  publication  of  the  Monograph, 
saw  a  rapid  extension  of  the  use  of  Proteals.  In  the  course  of  a 
lecture  tour  in  the  west  (April  12th  to  August  19th,  1917),  I 
delivered  over  one  hundred  addresses  on  Proteal  Therapy  to 
companies  of  medical  men,  emphasizing  always  the  wide  possi- 
bilities of  the  method  in  its  application  to  conditions  of  disturbed 
metabolism,  and  specifically  urging  the  use  of  the  Proteals  in 
anaemias,  toxaemias,  rheumatoid  conditions,  asthma,  and  tuber- 
culosis. Partly  as  a  result  of  this  personal  presentation,  several 
hundred  physicians  have  used  the  Proteals  in  these  and  allied 
conditions.  More  than  fourteen  thousand  ampules  of  the  vari- 
ous Proteals  were  sent  from  my  laboratory  to  the  members  of 
the  profession  for  such  use  during  the  year  1917  and  the  first 
two  months  of  1918. 

A  large  number  of  these  physicians  have  reported  gratifying 
experiences  in  the  use  of  the  Proteals,  notably  in  the  treatment 
of  anaemias,  rheumatoid  arthritis,  asthma,  and  tuberculosis; 
corroborating  in  a  most  satisfactory  way  my  personal  expe- 
rience. Some  of  these  reports  will  be  found  incorporated  in 
the  text  of  the  ensuing  pages ;  which  is  chiefly  devoted,  however, 
to  records  gained  in  my  own  office,  with  particular  emphasis 
on  my  original  hematological  studies.  The  experience  of  the 
co-operating  physicians,  nevertheless,  forms  a  most  enhearten- 
ing  background,  giving  assurance  that  the  pioneer  results  can  be 


126      THE   PROTEOMORPHIC  THEORY   AND  THE    NEW    MEDICINE 

duplicated  everywhere  in  the  hands  of  the  profession  at  large. 
The  "entirely  new  field  of  therapeutics"  covering  the  domain  of 
"all  protein  infections"  is  no  longer  an  unexplored  territory. 
Proteal  therapy  is  by  way  of  assuming  its  predicted  rank  along- 
side serum  therapy  and  vaccine  therapy,  and  the  suggestion  that 
it  may  ultimately  "altogether  outstrip  both  these  relatively  new 
additions  to  the  equipment  of  the  practical  physician"  seems  no 
longer  hazardous. 

If,  then,  making  prophecy  possible  is  the  final  test  of  the  truth 
of  a  theory,  the  Proteomorphic  theory  and  its  corollary,  the 
principle  of  the  Protein  Response  in  Therapeutics,  have  found 
abundant  justification.  I  think  I  am  speaking  well  within  bounds 
in  saying  that  there  are  few  instances  in  the  entire  history  of 
medicine  in  which  a  therapeutic  method  has  had  so  secure 
and  so  thoroughly  scientific  a  theoretical  foundation.  In  recog- 
nition of  this  fact,  it  would  perhaps  be  permissible  to  speak  of 
the  use  of  non-toxic  (non-specific)  proteins  as  antigens  in  dealing 
with  all  foreign  protein  invasions  and  inherent  disturbances  of 
protein  metabolism,  as  utilizing  and  representing  the  "Pro- 
teomorphic Principle." 

The  particular  application  of  this  principle,  which  will  chiefly 
claim  attention  in  the  succeeding  chapter — the  only  application, 
indeed,  which  has  been  tested  on  an  extensive  scale  up  to  the 
present  time — has  to  do  with  the  vegetable  proteins,  for  which 
I  have  suggested,  provisionally,  the  name  of  Proteals. 


CHAPTER  IV 
THE  SCIENCE  AND  ART  OF  PROTEAL  THERAPY 

If  the  testimony  presented  in  the  earlier  chapters  of  this 
book  is  accepted  as  conclusive,  it  will  be  understood  that  the 
most  salient  bodily  response  to  the  hypodermic  administration 
of  proteins  has  to  do  with  the  regeneration  of  the  blood. 

I  have  observed,  as  characteristic  and  almost  uniform  effects 
of  proteantigen  treatment,  increase  of  haemoglobin,  increase  in 
numbers  and  modification  in  quality  of  the  red  corpuscles,  and 
modification  of  the  white  corpuscles  in  the  direction  of  normal 
numbers,  relative  decrease  of  polynuclears,  and  relative  increase 
of  mononuclears,  in  particular  the  large  mononuclears,  and  of 
eosinophiles. 

These  modifications  of  the  blood  are  too  conspicuous  and  too 
uniform  to  be  considered  as  accidental.  They  have  been  ob- 
served in  a  considerable  variety  of  maladies,  including  simple 
anaemia,  secondary  anaemia,  pernicious  anaemia,  Graves'  disease, 
intestinal  toxaemia,  and  other  protein  toxaemias,  rheumatoid 
arthritis,  chronic  articular  rheumatism,  tuberculosis,  mastitis, 
and  cancer.  The  aggregate  number  of  cases  under  observation 
is  large  enough  to  justify  deductions  of  a  somewhat  definite 
character. 

The  original  studies,  and  up  to  the  present  by  far  the  most 
comprehensive  ones,  bearing  on  this  subject  have  been  made  by 
the  writer  himself  or  under  his  immediate  personal  supervision ; 
but  corroborative  testimony  as  to  individual  cases  has  come 
from  many  independent  sources,  telling  of  observations  of  physi- 
cians who  have  administered  the  proteal  treatment  to  patients 
suffering  from  a  variety  of  maladies.  In  particular  these  observa- 
tions have  had  to  do  with  the  improvement  in  haemoglobin  and 
the  increase  of  the  red  blood  count;  since  a  good  many  physi- 
cians make  observation  of  these  matters  without  taking  time 
to  make  careful  differential  leucocyte  count.  It  is  hoped  that 
physicians  in  general  will  pay  more  attention  in  the  near  future 
to  the  blood  count  in  general  and  the  leucocyte  count  in  partic- 
ular, partly,  at  least,  as  a  result  of  the  evidence  presented  in  my 
cancer  Monograph  and  in  the  present  volume. 

Meantime  practitioners  who  have  not  facilities  for  careful 
blood  examinations  may  observe  the  clinical  effects  of  the  use 
of  the  new  method,  which  after  all  is,  in  the  last  analysis,  the 
matter  of  genuine  importance.  If  the  patient  looks  better,  feels 
better,  has  improved  appetite  and  digestion,  sleeps  better,  gains 

127 


128      THE    PROTEOMORPHIC   THEORY   AND   THE    NEW    MEDICINE 

in  weight,  strength  and  energy — practitioner  and  patient  alike 
will  indulge  a  measure  of  satisfaction  quite  independent  of  any 
microscopical  findings  to  justify  their  clinical  observations. 
Nevertheless  I  would  urge  that  the  most  intelligent  administra- 
tion of  protein  therapy  cannot  be  carried  out  without  the  aid 
of  the  microscope,  for  reasons  that  have  been  detailed  in  earlier 
chapters.  This  is  particularly  true,  as  I  have  pointed  out,  in 
the  later  stages  of  treatment.  The  initial  doses  of  any  Proteal 
may  be  given  after  a  routine  method,  details  of  which  will  be 
presented  more  fully  in  a  moment.  But  determination  of  dosage 
at  a  later  stage  of  treatment,  particularly  in  case  of  grave  mala- 
dies, and  questions  as  to  the  time  when  treatment  may  advan- 
tageously be  discontinued  should  be  answered  by  combining 
clinical  observations  with  microscopic  study  of  the  blood.  I 
repeat,  however,  that  such  observation  is  not  absolutely  necessary, 
any  more  than  it  is  in  connection  with  any  other  line  of  treat- 
ment. But  my  own  studies  lead  me  to  feel,  in  common  with  other 
hematologists,  that  the  microscope  should  be  given  a  far  more 
important  place  in  the  equipment  of  the  general  practitioner 
than  has  yet  been  accorded  it,  and  I  would  not  overlook  this 
opportunity  to  reiterate  that  opinion. 

I  would  urge  the  practitioner  to  carry  his  studies  of  the  blood 
somewhat  beyond  the  elementary  stage,  and  I  venture  to  make 
a  few  practical  suggestions  based  on  my  own  personal  studies 
before  going  on  to  a  detailed  consideration  of  the  practicalities 
of  the  administration  of  proteals.  I  am  stimulated  to  do  this 
partly  because  a  large  correspondence  with  physicians  has  shown 
a  growing  interest  in  the  subject,  and  I  feel  that  by  presenting 
the  matter  here  I  can  in  effect  answer  individual  inquiries  as 
advantageously  as  by  personal  letter.  What  I  have  to  say  here, 
however,  must  not  be  taken  as  a  comprehensive  study,  but  only 
as  a  series  of  practical  hints. 

At  the  outset,  I  would  ^suggest  that  a  good  deal  more  atten- 
tion might  advantageously  be  given  to  cells  in  the  counting  cham- 
ber than  is  commonly  done.  A  mere  numerical  count  does  not 
by  any  means  tell  the  entire  story.  It  is  often  of  interest  and 
value  to  note  the  response  of  the  cells  to  the  influence  of  the 
Toisson  solution  that  is  commonly  used  in  counting.  Often  cells 
that  at  first  seem  round,  full,  and  normal  will  presently  show 
crenated  edges,  shrivel  in  size,  develop  spine-like  processes  or 
fimbriations  until  they  assume  the  appearance  of  diminutive  sea 
urchins,  and  show  other  malformations. 

It  is  my  opinion  that  the  time  required  to  bring  about  these 
modifications  gives  at  least  general  clues  to  the  qualitative  status 
of  the  red  corpuscles;  and,  in  particular,  that  the  corpuscles 
suffering,  from  protein  toxaemia  (intestinal,  cancerous,  or  what 


THE   SCIENCE   AND  ART  OF   PROTEAL   THERAPY  129 

not)  usually  show  an  exceptional  sensitiveness,  their  bodies  be- 
coming malformed  in  the  course  of  a  few  minutes  or  a  half  hour 
even  though  showing  normal  appearance  when  the  blood  is  first 
drawn.  The  proportion  of  cells  that  take  on  the  sea  urchin 
form  should  also  be  noted  as  giving  a  general  impression  of  the 
degree  of  abnormality. 

Sometimes  it  happens  that  under  Proteal  treatment  the  red 
corpuscles  show  a  very  marked  betterment  in  size  and  form,  so 
that  there  is  notable  increase  in  the  bulk  of  these  corpuscles  in 
the  aggregate,  although  the  actual  number  may  be  decreased. 
An  interesting  illustration  of  this  is  shown  by  a  case  of  cancer 
of  the  stomach  under  treatment  at  my  office,  patient  No.  543. 
When  first  examined,  before  treatment,  the  blood  of  this  patient 
showed  4,900,000  red  corpuscles,  but  the  great  majority  of  these 
were  mere  fragments  of  normal  corpuscles,  distorted  and  mis- 
shapen, three  or  four  of  them  scarcely  equaling  the  bulk  of  a 
normal  corpuscle.  The  haemoglobin  index  was  only  60,  and  the 
appearance  of  the  patient  was  cachetic  to  the  point  of  ghastliness. 
The  white  cells  numbered  13,000. 

After  one  week  of  treatment  with  Proteal  No.  37  (chiefly  pro- 
teins of  mustard  seed,  alfalfa  seed,  and  alfalfa  meal)  there  was 
a  very  striking  modification  in  the  character  of  the  red  cor- 
puscles, the  dark  fragments  having  disappeared  in  the  main 
and  their  place  being  taken  by  corpuscles  of  fairly  normal  size 
and  appearance.  The  numerical  count,  however,  had  dropped 
to  4,364,000.  Meantime  the  white  cells  had  been  reduced  to 
8,500. 

The  haemoglobin  index  was  now  75. 

At  the  end  of  the  second  week,  90  per  cent,  of  the  red  cells 
were  normal  in  size  and  fairly  regular  in  contour,  except  that  a 
good  many  were  somewhat  oval  in  shape.  Many  of  the  cells 
were  slightly  fringed  at  the  edges,  and  there  were  a  few  small 
cells  and  a  good  many  platelets.  In  general  the  red  cells  were 
recorded  as  presenting  an  utterly  different  aspect  from  the  field 
of  two  weeks  earlier — a  tremendous  advance  towards  normality. 
The  total  number,  however,  was  only  4,120,000.  The  white  cells 
numbered  7,200. 

At  the  end  of  the  third  week  there  was  farther  advance  in 
the  same  direction  as  regards  the  quality  of  cells. 

At  the  end  of  the  fourth  week,  this  patient's  red  corpuscles 
showed  not  more  than  10  per  cent,  of  the  crenated  and  mis- 
shapen corpuscles  after  standing  two  hours  in  the  Toisson 
fluid.  A  large  proportion  of  the  cells  were  full  sized  and  fairly 
normal  in  appearance.  And  the  number  had  gone  up  again  to 
4,954,000.  Meantime  there  had  been  a  further  decrease  in  the 
white  corpuscles,  which  now  numbers  6,130.  The  haemoglobin 


130      THE   PROTEOMORPHIC  THEORY   AND  THE   NEW    MEDICINE 

index  had  advanced  week  by  week  from  the  initial  60  to  70, 
70  plus,  and,  at  the  end  of  the  third  week,  80.  Modifications 
of  the  differential  count  and  of  the  qualitative  status  of  the  white 
cells  will  be  referred  to  in  another  connection.  Here  it  suffices 
to  say  that  these  were  of  the  usual  character,  involving  increase 
of  the  large  monocytes  and  a  characteristic  change  in  the  staining 
quality  of  the  cells. 

It  is  perhaps  not  unimportant  to  add  that  the  patient  showed 
steady  improvement  in  his  clinical  condition,  as  might  be  ex- 
pected considering  the  blood  changes.  And  it  should  be  ex- 
plained that  the  cancer  involves  the  pyloris,  closing  the  aperture, 
and  that  a  gastro-enterostomy  making  an  artificial  exit  through 
the  anterior  wall  of  the  stomach  had  been  performed  about  five 
months  before  the  Proteal  treatment  was  begun,  the  surgeons 
at  that  time  reporting  themselves  unable  to  remove  the  cancerous 
mass,  which  involved  not  only  the  stomach  but  the  liver.  Since 
that  time,  prior  to  beginning  the  Proteal  treatment,  the  patient 
had  been  given  the  usual  variety  of  drugs,  including  iron  and 
arsenic,  together  with  sedatives,  yet  he  had  gone  from  bad  to 
worse,  suffered  constantly  from  gastric  disturbances  and  the 
regurgitation  of  a  bitter  greenish  fluid.  He  was  constantly 
hungry,  no  matter  how  much  food  he  took,  and  had  wasted 
away  until,  although  more  than  six  feet  high,  he  weighed  only 
128  Ibs.  Could  sleep  little  owing  chiefly  to  discomfort  in  con- 
nection with  the  joints  of  his  legs.  The  left  knee  joint  was 
much  swollen,  and  the  patient  limped  markedly  in  attempting  to 
walk. 

When  the  patient  came  under  my  observation  all  drugs  taken 
by  the  stomach  were  discontinued  except  that  rhubarb  and  soda 
mixture  was  given,  together  with  a  daily  dose  of  mineral  oil  to 
aid  in  regulating  the  bowels,  which  had  been  obstinately  con- 
stipated. The  patient  was  placed  on  an  exclusively  vegetable 
and  milk  diet,  and  Proteal  hypodermics  were  administered  daily 
in  doses  beginning  with  3  minims  and  advancing  pretty  rapidly 
to  a  maximum  of  15  minims.  The  response  was  prompt  and 
stimulative.  The  patient  soon  handled  his  food  better  and  he 
gained  steadily  in  strength,  presently  going  about  by  himself  as 
he  had  not  done  for  some  time  before.  The  knee  joints  showed 
quite  an  increase  in  swelling  at  first,  but  before  ten  days  and 
subsided  to  practically  normal,  and  the  discomfort  in  the  legs 
had  disappeared,  so  that  the  patient  was  sleeping  well.  His  com- 
plexion changed  quite  conspicuously,  as  would  be  expected, 
considering  the  modification  in  the  blood,  and  his  mental  state 
was  far  more  comfortable.  Meantime  palpation  showed  marked 
flattening  of  the  gastric  mass,  which  was  hollowed  conspicuously 
equatorially,  and  which  became  slightly  tender  on  pressure,  as 


THE   SCIENCE   AND  ART  OF   PROTEAL  THERAPY  131 

it  had  not  been  before.  The  patient  mentioned  also  having 
occasionally  experienced  a  gnawing  sensation  in  the  region  of 
the  mass,  not  especially  disagreeable  in  character,  but  sufficient 
to  attract  attention. 

I  have  cited  details  of  this  case  because  it  is  fairly  typical. 
That  the  striking  modifications  of  blood  and  the  attendant 
clinical  evidences  of  improvement  were  due  directly  to  the  ad- 
ministration of  the  vegetable  protein,  seems  scarcely  open  to 
doubt.  It  is  perhaps  equally  open  to  doubt  whether  any  other 
treatment  hiherto  available  could  be  expected  to  produce  modi- 
fications similar  in  character  in  a  late  stage  of  carcinoma  of  the 
stomach  which  had  brought  its  victim  seemingly  to  the  verge 
of  moribundity. 

In  such  a  case  as  this,  it  may  be  said  that  observation  of  the 
blood  in  the  counting  chamber  served  to  give  corroborative  evi- 
dence rather  than  as  a  guide  in  treatment.  It  should  be  pointed 
out,  however,  that  at  a  later  stage  in  such  cases  the  microscope 
may  give  the  crucial  indication  as  to  the  time  when  it  is  desirable 
to  change  the  character  of  the  protein,  substituting  a  new  pro- 
teal  for  the  one  which  is  losing  its  effect.  Moreover,  in  many 
cases  in  which  the  protein  toxaemia  is  of  more  equivocal  char- 
acter— anaemias  of  doubtful  origin,  mild  intestinal  toxaemia, 
etc. — the  microscope  may  give  unequivocal  evidence,  through  ob- 
servation of  the  modification  of  the  red  cells  above  referred  to, 
that  will  be  of  a  great  value  in  diagnosis  and  thereby  aid  in  de- 
termining the  probable  availability  of  proteal  treatment. 

Here,  for  example,  is  a  patient  having  tumorous  masses  in 
both  breasts.  Her  physician  has  urged  her  to  have  an  immediate 
operation  for  the  amputation  of  both  breasts.  But  examination 
of  the  blood  shows  only  3,200,000  red  corpuscles,  with  extreme 
leukopenia,  the  white  cells  numbering  but  1,800. 

With  such  blood  conditions,  one  could  not  justify  an  operation 
without  preliminary  Proteal  treatment.  The  response  to  this 
treatment  was  immediate  and  extraordinary.  After  ten  days 
the  red  corpuscles  had  increased  to  5,716,000,  and  the  white 
corpuscles  to  8,400.  The  patient's  general  appearance  and  sub- 
jective feelings  had  been  metamorphosed.  From  having  been 
depressed  and  lethargic,  she  became  exhilarated  and  buoyant. 
She  declared  that  she  felt  like  a  girl.  Presently  her  condition 
was  considered  suitable  for  an  operation,  and  the  removal  of 
the  breasts  was  accomplished,  followed  by  an  uneventful  re- 
covery. After  leaving  the  hospital,  however,  the  patient  did 
not  recover  her  strength  rapidly.  Two  weeks  after  the  opera- 
tion, it  was  found  that  the  red  blood  count  was  4,516,000.  This 
was  satisfactory  enough,  but,  on  the  contrary,  the  white  count 
showed  16,500,  obviously  much  too  high.  The  Proteal  treat- 


132      THE   PROTEOMORPHIC  THEORY   AND  THE   NEW    MEDICINE 

merit,  which  had  been  interrupted  a  few  days  before  the  opera- 
tion, was  now  resumed.  Six  days  later  the  blood  count  showed 
the  following:  red  corpuscles,  4,740,000;  leucocytes,  13,500,— 
telling,  obviously,  of  progress  in  the  right  direction.  The  haemo- 
globin index  had  increased  from  80  to  95.  Clinically,  there  was 
immediate  betterment  associated  with  the  resumption  of  the 
proteal  treatment ;  the  patient  ceased  to  have  fainting  spells,  and 
gained  strength  progressively. 

It  must  be  obvious  that  the  microscope  is  an  invaluable  auxil- 
iary in  helping  to  determine  the  line  of  treatment  in  such  a  case 
as  this.  The  same  thing  is  true,  as  is  equally  obvious,  of  cases  of 
anaemia  of  various  types,  and  in  particular  of  intestinal  and  other 
protein  toxaemias,  the  clinical  symptoms  of  which  may  be  varied 
and  lacking  in  pathognomonic  character. 

If  we  turn  from  the  counting-chamber  to  the  blood  smear  we 
find  a  further  exemplification  of  the  same  principle.  Here  the 
red  cells  are  still  of  interest  as  regards  their  size,  form,  and 
tendency  to  dry  with  smooth  contour  or  with  crenated  edges 
suggestive  of  amoeboid  activity.  Their  tendency  to  take  on  a 
copper  color  on  one  hand  or  a  bluish  cast  on  the  other  in  the 
ordinary  Wright  or  Hastings  stain  (methylene  blue  and  cosine) 
may  indicate  a  condition  of  alkalinity  or  acidity  as  the  case  may 
be  that  gives  at  least  suggestive  hints  as  to  like  conditions  in 
the  patient's  system.  The  presence  or  absence  of  a  tendency  to 
rupture,  with  the  formation  of  so-called  platelets,  is  also  of 
interest,  as  suggesting  the  degree  of  pliability  of  the  cells  and 
the  liquidity  of  their  contents. 

According  to  my  own  observations,  for  example,  the  red  cells 
of  late  stage  cancer  subjects  are  of  such  constitution  that  they 
do  not  tend  to  disrupt  and  produce  a  normal  equipment  of 
platelets  on  the  smear.  This  is  consonant  with  the  tests  made 
some  years  ago  at  the  Loomis  Laboratory,  which  showed  that 
the  red  cells  of  cancer  subjects  are  more  resistant  to  haemolysis 
than  normal  cells.  I  regard  the  appearance  of  platelets  in  normal 
numbers  under  treatment  as  a  favorable  indication ;  tending  at 
least  to  suggest  that  a  modification  of  the  chemical  constitution 
of  the  cells  is  being  made  in  the  direction  of  normality. 

Vacuolation  of  center  of  the  red  cell,  indicative  of  paucity  of 
haemoglobin,  and  the  presence  or  absence  of  normoblasts  are 
conditions  that  will  be  observed  as  a  matter  of  course.  It  is 
not  always  easy  to  interpret  the  precise  meaning  of  influx  of 
normoblasts.  I  have  known  it  to  occur  in  an  individual  previously 
in  apparent  health  and  undergoing  no  treatment  whatever,  in  con- 
nection with  the  onset  of  an  acute  coryza  that  did  not  go  on  to 
a  stage  of  marked  infection.  In  the  particular  case  that  I  have 
in  mind  there  was,  however,  an  accompanying  jump  in  the 


THE   SCIENCE  AND  ART  OF   PROTEAL  THERAPY  133 

leucocyte  count  from  5,800  to  13,000,  showing  that  the  infection 
was  really  more  significant  than  the  clinical  symptoms  might 
have  suggested.  Obviously  there  was  a  marked  stimulus  to  the 
blood-forming  organs.  An  interesting  feature  of  this  case  is 
that  the  presence  of  normoblasts  and  of  amoeboid  red  cells  taking 
a  coppery  stain  was  observed  two  days  before  the  onset  of  the 
symptoms  of  what  appeared  to  be  an  incipient  influenza,  which, 
however,  proved  abortive. 

While  the  observation  of  the  red  cells  On  the  smear  may  thus 
give  items  of  highly  interesting  and  important  information,  it 
goes  without  saying  that  the  chief  interest  of  the  smear  resides 
in  the  observation  of  the  white  corpuscles.  No  one  who  has  read 
the  earlier  chapters  of  this  book  needs  to  be  told  that  I  regard 
the  differential  count  as  of  supreme  importance.  But  I  would 
emphasize  the  fact  that  a  good  many  illuminative  things  are  to 
be  learned  from  careful  observation  of  the  leucocytes,  connoting 
their  size,  form,  staining  qualities,  tendency  to  agglutinate,  and 
the  like,  quite  without  reference  to  the  differential  count,  or,  better 
stated,  as  supplementary  to  that  count. 

It  is  a  not  unfamiliar  experience,  for  example,  that  a  series 
of  slides  obtained  under  closely  similar  conditions  of  technique, 
and  with  the  same  stain,  show  striking  modifications  of  the 
color  reaction  of  the  white  corpuscles.  One  slide  may  show 
corpuscles  that  scarcely  take  the  stain  at  all ;  a  second  shows  the 
nuclei  with  a  deep  bright  blue  stain;  a  third  shows  corpuscular 
nuclei  of  a  purplish  color. 

Assuming  that  the  stain  used  is  one  of  the  varieties  of  the 
methylene  blue  and  cosine  combination  (Hastings',  for  example), 
it  may  be  accepted,  I  believe,  that  the  cells  showing  the  purplish 
nuclei  are  the  ones  that  more  closely  approximate  the  normal. 
On  the  other  hand,  the  cells  that  take  the  bright  blue  stain  are 
somewhat  characteristic  of  conditions  in  which  there  is  known  to 
be  very  marked  disturbance  of  protein  metabolism  (for  example 
late  stage  cancer),  and  I  have  come  to  regard  them  as  in  a 
measure  pathognomonic  of  disturbed  protein  metabolism,  how- 
ever superinduced.  As  suggesting  this  condition,  they  are,  I 
believe,  of  distinct  diagnostic  value. 

It  is  natural  to  assume  that  cells  that  take  the  blue  stain  have 
an  exceptionally  acid  quality,  since  they  show  an  affinity  for 
the  basic  dye.  Frequently  such  cells  show  cytoplasm  in  which 
the  esinophile  granules  of  the  normal  cell  are  invisible  or  but 
very  faintly  revealed. 

I  have  frequently  observed  that  cells  that  show  these  qualities 
have  a  tendency  to  agglutinate  or  clump  together.  Not  infre- 
quently a  smear  may  show  the  entire  leucocyte  population  scat- 
tered into  a  windrow  at  the  end,  even  though  the  red  corpuscles 


134      THE   PROTEOMORPHIC  THEORY   AND  THE   NEW    MEDICINE 

may  be  evenly  distributed  throughout  the  length  of  the  smear. 
One  may  assume  that  corpuscles  that  show  this  propensity  have 
exceptional  cohesive  properties,  suggesting  a  modification  of 
their  chemical  constitution.  Of  course  the  amount  of  pressure 
exerted  by  the  spreading  slide  will  modify  the  distribution  of 
the  white  corpuscles  under  any  condition,  and  in  general  it  may 
be  expected  that  the  larger  cells,  notably  the  large  monocytes  and 
eosinophiles,  will  tend  to  be  distributed  farther  down  the  smear 
than  the  average  small  lymphocyte.  These  variations  must  be 
borne  in  mind;  but  the  experienced  hematologist  is  not  likely  to 
confound  modifications  of  distribution  of  the  corpuscles  due  to 
changes  in  his  technique  with  modifications  connoting  variant 
systemic  conditions  of  the  patient. 

If  there  were  any  doubt  as  to  this,  one  may  satisfy  oneself 
that  the  color  reactions  and  agglutination  qualities  of  the  white 
corpuscles  represent  actual  differences  of  systemic  conditions  by 
making  a  series  of  slides  of  three  or  four  patients  in  succession, 
with  three  or  four  slides  to  each  patient.  It  may  then  be  seen 
that  there  are  marked  and  characteristic  differences  distinguish- 
ing each  group,  lying  entirely  aside  from  the  minor  variations 
among  slides  from  the  same  patient. 

Not  infreuently  a  slide  that  shows  the  blue-stain  nuclei  may 
show  other  white  corpuscles  that  scarcely  take  the  stain  at  all ; 
or  corpuscles  of  the  lymphoidocyte  and  plasma  cell  order,  in 
which  the  nucleus  remains  practically  unstained  while  the  cyto- 
plasm takes  a  deep  basic  stain.  There  is,  I  believe,  a  qualitative 
rather  than  a  class  distinction  between  these  two  types  of  cells, 
— namely,  those  that  take  the  blue  stain  distinctly  and  those 
that  show  exceedingly  faint  nuclei  with  or  without  basophile 
cytoplasm.  As  I  interpret  it,  these  are  varying  conditions  of  ab- 
normal acidity  of  the  cell,  associated  with  a  greater  or  less  degree 
of  activity,  or  a  different  stage  of  activity,  in  the  hydrolyzing 
of  a  foreign  or  abnormal  protein  content.  The  fact  that  the 
cells  spoken  of  as  lymphoidocytes  and  plasma  cells,  and  charac- 
terized by  unstained  nuclei  and  deep-stained  cytoplasm,  are  in 
effect  aberrant  types  of  large  monocytes  and  small  lymphocytes 
respectively  adds  color  to  this  interpretation,  provided  of  course 
the  Proteomorphic  conception  which  ascribes  to  the  mononuclear 
cells  a  chief  share  in  dealing  with  foreign  proteins  is  accepted. 

Theories  aside,  however,  the  observed  variations  of  cellular 
conditions,  as  regards  staining  properties,  give  important  clues 
to  the  condition  of  the  patient.  Moreover,  interesting  modifica- 
tions of  these  conditions,  in  a  predictable  direction,  may  be  ex- 
pected in  connection  with  proteal  medication. 

A  typical  case  in  point  is  that  of  patient  No.  543,  cancer  of 
the  stomach,  whose  red  cell  count  was  above  referred  to.  When 


THE   SCIENCE  AND  ART   OF   PROTEAL  THERAPY  135 

this  patient's  blood  was  examined  before  treatment,  it  is  found 
that  the  leucocytes  stained  with  very  blue  nuclei,  many  of  them 
taking  the  stain  very  badly.  Lymphoidocytes  and  plasma  cells 
largely  took  the  place  of  normal  cells.  There  were  no  normo- 
blasts,  and  no  platelets.  After  a  week  of  Proteal  treatment,  the 
entire  character  of  the  white  cells  had  changed.  The  record 
reads:  "Polynuclears  stained  beautifully,  with  purple  nuclei; 
cytoplasm  granular,  moderately  acidophile.  All  lymphocytes 
stained  typically.  No  lymphoidocytes  or  plasma  cells.  A  very 
normal  collection  of  white  cells,  beautifully  stained.  Numerous 
big  typical  large  monocytes.  Occasional  normoblasts,  platelets 
numerous." 

Two  weeks  later  further  modifications  in  the  same  direction 
had  taken  place.  The  white  cells  were  evenly  distributed  in  the 
smear,  except  that  a  few  very  large  monocytes  and  myelocytes, 
owing  to  their  bulk,  dragged  toward  the  end.  Nuclei  took  a 
normal  purple  stain,  the  cytoplasm  of  the  polynuclears  conspic- 
uously red-granuled.  Platelets  were  now  fairly  abundant,  and 
normoblasts  absent  or  extremely  rare. 

It  is  impossible  not  to  associate  such  modifications  of  the 
cells  with  the  marked  improvement  in  clinical  symptoms  mani- 
fested by  the  patient.  When  one  has  seen  similar  modifications 
take  place  under  Proteal  treatment  again  and  again,  the  belief 
that  there  is  a  causal  relation  between  the  administration  of  the 
Proteals  and  the  changed  blood  condition,  and  that  the  improved 
clinical  conditions  are  effects  and  not  accidental  concomitants, 
becomes  a  firm  conviction. 

If  the  subject  to  whom  the  protein  extract  is  administered  is, 
let  us  say,  a  patient  with  cancer  of  the  uterus,  associated  with 
pain,  a  fcetid  discharge,  and  marked  cachexia,  there  is  likely  to 
be  a  very  notable  modification  of  symptoms.  The  pain  may 
largely  disappear  after  two  or  three  treatments;  the  character 
of  the  discharge  may  be  so  modified  that  it  becomes  watery  and 
inodorous ;  and  the  general  physical  condition  of  the  patient  may 
be  strikingly  modified  in  a  favorable  direction.  As  the  treatment 
continues,  the  neoplasm  itself  may  undergo  a  conspicuous  and 
unequivocal  regression  to  a  greater  or  less  extent. 

Similar  modifications  may  be  observed  in  malignant  neoplasms 
of  various  types  wherever  located  in  the  body.  There  remains, 
however,  the  highly  interesting  question  as  to  how  such  changes 
are  brought  about  by  the  hypodermic  administration  of  small 
quantities  of  vegetable  proteins. 

MODIFICATIONS  OF  THE  LEUCOCYTE  COUNT 

A  further  clue  to  the  answer  is  found  in  the  fact  that  con- 
spicuous modifications  of  the  leucocyte  count  no  less  than  of  the 


136      THE   PROTEOMORPHIC   THEORY   AND  THE   NEW    MEDICINE 

red  cell  count  almost  invariably  follow  the  administration  of  the 
proteins.  These  changes  are  of  a  kind  susceptible  of  interpreta- 
tion in  terms  of  the  Proteomorphic  theory.  But  they  have  a 
high  degree  of  interest  quite  aside  from  theoretical  interpreta- 
tions. As  gauged  by  the  study  of  about  200  original  cases, 
they  appear  to  include  a  tendency  to  bring  the  polynuclear  leu- 
cocytes and  small  lymphocytes  towards  the  normal ;  whereas  the 
basophiles  and  eosinophiles  are  markedly  increased,  and  the  large 
monocytes  are  increased  by  several  hundred  per  cent. 

Before  giving  details  as  to  these  interesting  modifications  of 
the  blood  count  brought  about  by  the  administration  of  protein 
antigens,  I  would  again  call  attention  to  the  highly  interesting 
laboratory  experiments  reported  by  Drs.  M.  W.  Man  waring  and 
Yoshio  Kusama,  of  the  department  of  bacteriology  and  immunity 
of  Leland  Stanford,  Jr.,  University,  as  recorded  in  the  Proceed- 
ings of  the  Society  for  Experimental  Biology  and  Medicine,  of 
May  24,  1916.  These  experiments  go  to  show  that  the  blood 
corpuscles  of  a  rabbit  actively  absorb  goat  serum  protein,  whether 
the  goat  serum  is  mixed  with  the  (defibrinated)  rabbit's  blood  in 
a  receptacle  outside  the  body  or  whether  it  is  injected  into  the 
system  of  the  living  rabbit. 

This  -observation,  obviously,  gives  strong  support  to  the  as- 
sumption of  the  Proteomorphic  theory  that  the  blood  corpuscles 
are  the  chief  agents  concerned  in  dealing  with  foreign  proteins 
— the  assumption  that  forms  the  chief  basis  for  the  explanation 
of  the  therapeutic  action  of  the  protein  remedies  with  which  the 
present  book  is  concerned. 

In  attempting  to  interpret  the  meaning  of  the  observed  changes 
in  the  blood  picture,  however,  one  is  entering  quite  unexplored 
territory,  and  a  territory  in  which  the  newly  observed  facts  do 
not  at  all  times  serve  as  an  accurate  guide. 

Interesting  hints  as  to  the  mutual  relations  of  the  various  types 
of  white  corpuscles  are  given  by  charts  in  which  the  different 
groups  of  cells  are  represented  by  graphic  lines  (see  the  cancer 
Monograph).  It  is  hoped  that  the  study  of  these  in  connection 
with  the  protein  remedies  will  throw  new  light  on  the  obscure 
relations  of  the  different  types  of  leucocytes.  When  a  much 
larger  series  of  charts  is  available  than  at  present,  it  is  certainly 
to  be  expected  that  relations  will  be  observed  between  the  mutual 
rise  and  fall  of  the  different  types  of  corpuscles  under  treat- 
ment that  will  help  to  explain  the  genetic  relations  of  these  bodies. 

In  making  such  charts,  it  is  desirable  to  transform  percentages 
of  the  differential  leucocyte  count  to  actual  numbers.  When  this 
is  done,  one  is  impressed  with  the  general  observation  that  there 
seems  a  strong  tendency,  under  the  Ptoteal  treatment,  for  the 
polynuclear  leucocytes  and  the  small  lymphocytes  to  be  modified 


THE   SCIENCE  AND  ART  OF  PROTEAL  THERAPY  137 

in  number  so  that,  after  treatment  has  been  continued  for  a  time, 
they  fall  within  normal  limits.  Here,  for  example,  is  one  chart 
(Case  No.  332)  in  which  at  the  outset  the  number  of  neutrophiles 
was  5,328,  and  the  number  of  small  lymphocytes  2,131 ;  these 
numbers  representing  in  each  case  an  excess  above  the  maximum 
normal  limits,  as  usually  computed.  But  after  treatment  had 
extended  over  about  90  days,  it  was  observed  that  the  polynu- 
clears  numbered  4,356,  and  the  small  lymphocytes  1,824;  both 
these  numbers  representing  a  (high)  normal  count. 

But  in  the  meantime,  it  should  be  noted  that  the  large  mono- 
cytes,  which  at  the  outset  numbered  1,420,  had  increased  to  2,403. 
The  original  count  is  far  in  excess  of  the  normal  (which  seldom 
exceeds  400),  and  the  final  count  exceeds  the  maximum  normal 
limits  by  600  per  cent.  The  assumption  is,  according  to  the  pres- 
ent thesis,  that  before  treatment  the  large  monocytes  had  been 
stimulated  to  excessive  production  under  influence  of  the  disin- 
tegrated cancer  cells;  and  that  the  protein  treatment  effected  a 
further  stimulation. 

A  similar  proportionate  increase  in  the  eosinophiles  has  taken 
place,  there  being  none  noted  at  all  before  treatment  and  the 
number  having  risen  almost  continuously  until  356  were  noted  at 
the  later  count, — about  double  the  normal  maximum  limit. 

Whatever  the  interpretation  put  upon  these  facts,  it  would 
appear,  as  already  pointed  out,  that  such  a  super-normal  count 
of  large  monocytes  and  eosinophiles  constitutes  a  favorable 
condition  in  the  organism  associated  with  improved  general 
health  of  the  patient  and  a  tendency  to  combat  the  cancer  cells 
effectively.  Indeed,  I  never  feel  that  the  desired  results  are 
being  attained  unless  this  characteristic  response  is  observed. 

Another  chart  illustrates  the  same  principle  in  a  different  way; 
inasmuch  as  it  was  necessary  to  increase  the  number  of  neutro- 
philes in  order  to  bring  them  to  a  high  normal  limit.  It  will  be 
observed  in  this  chart  (Case  No.  369)  that  at  the  outset  the 
neutrophiles  numbered  4,190  and  the  small  lymphocytes  2,630. 
At  the  end  of  three  weeks'  treatment,  the  polynuclears  had  risen 
to  4,935,  and  the  small  lymphocytes  had  dropped  to  1,410.  Here, 
as  before,  the  final  count  shows  polynuclears  and  small  lympho- 
cytes within  normal  limits. 

In  the  meantime,  in  this  second  chart,  as  in  the  first,  the  large 
monocytes  have  risen  conspicuously;  in  this  case  from  1,150  to 
2,608 ;  and  the  eosinophiles  have  increased  from  213  to  329.  The 
numbers  here  are  substantially  in  accord  with  those  shown  in 
the  other  chart.  Such  close  agreement  is  a  matter  of  coincidence, 
although  the  same  general  principle  will  be  seen  reiterated  in  a 
large  number  of  cases. 

A  striking  feature  of  both  these  charts  is  the  marked  modifi- 


138      THE    PROTEOMORPHIC   THEORY    AND   THE    NEW    MEDICINE 


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THE   SCIENCE   AND   ART   OF   PROTEAL  THERAPY  139 

cation  in  the  number  of  neutrophiles  and  small  lymphocytes  from 
the  initial  dose  of  the  vegetable  protein.  A  question  not  unnat- 
urally arises  as  to  whether  there  is  any  mutual  relation  between 
the  two  groups  of  leucocytes,  or  whether  the  modification  of  their 
numbers  has  been  brought  about  independently.  Glancing  at  the 
first  chart,  one  might  think  that  there  must  be  some  mutual  rela- 
tion, inasmuch  as  the  lines  showing  modification  of  the  neutro- 
philes run  almost  parallel  with  those  showing  modification  of  the 
small  lymphocytes.  But  in  the  second  chart,  we  find  that  the 
slope  of  the  line  is  reversed,  the  neutrophiles  showing  a  rapid  rise 
after  the  first  dose  and  the  lymphocytes  a  rapid  decline. 

It  is  not  impossible  to  frame  a  theory  that  would  harmonize 
these  seemingly  contradictory  results,  but  perhaps  it  is  not  worth 
while  to  attempt  to  do  so  at  the  moment.  Our  chief  present  con- 
cern is  with  the  observed  facts,  which  fortunately  are  unequiv- 
ocal. As  above  outlined,  these  include  a  notable  departure  from 
the  normal  blood  picture  brought  about  by  the  administration  of 
the  protein  remedies  as  evidenced  in  a  relatively  enormous  in- 
crease of  the  larger  monocytes,  a  conspicuous  increase  of  the 
eosinophiles  and  basophiles ;  and  a  tendency  to  bring  the  small 
lymphocytes  and  the  neutrophiles  within  normal  bounds. 

By  way  of  recapitulation,  it  is  well  to  recall  that  Vaughan's 
experiment  seems  to  show  that  the  specific  enzymes  of  the  large 
mononuclears  have  particular  value  in  proteolyzing  the  cancer 
proteins.  Stated  otherwise,  the  large  mononuclears  would  seem 
to  have  particular  affinity  for  cancer  proteins ;  which  is  only  an- 
other way  of  saying,  probably,  that  they  are  particularly  adapted 
to  deal  with  proteins  of  an  embryonic  type.  The  fact  that  the 
large  mononuclears  abound  relatively  in  the  normal  blood  of  the 
child  may  be  recalled  in  this  connection. 

BLOOD  CHANGES  IN  TUBERCULOSIS 

Many  instances  of  spectacular  changes  in  the  corpuscular  rela- 
tions under  Proteal  treatment  are  given  in  the  cancer  Mono- 
graph. Here  it  is  desirable  to  supplement  these  records  by 
citing  a  few  cases  representing  maladies  of  different  types. 

Here,  for  example,  is  the  case  of  J.  G.,  a  patient  in  the  late 
stages  of  tuberculosis  of  the  lungs.  Left  lung  solidified.  Gen- 
eral condition  extremely  cachectic,  so  emaciated  and  frail  that 
his  tenure  of  life  seemed  very  uncertain.  His  blood  showed 
3,260,000  red  corpuscles  of  exceedingly  poor  quality, — variant 
in  size,  malformed  in  shape.  The  white  corpuscles  numbered 
14,500,  of  which  87  per  cent,  were  polynuclears,  7.3  per  cent, 
small  lymphocytes  (including  plasma  cells),  and  5.6  per  cent, 
large  mononuclears.  The  polynuclears  are  recorded  as  of  red- 


140      THE   PROTEOMORPHIC  THEORY   AND  THE   NEW    MEDICINE 

purple  nuclei,  not  sharply  defined  from  the  cytoplasm,  which  was 
opalescent,  and  distinctly  reddish.  The  large  monocytes  were 
typical,  dark,  with  opaque  cytoplasm. 

This  patient  was  not  treated  in  my  office,  but  by  an  associated 
physician,  and  a  second  blood  count  was  not  made  for  six  weeks, 
at  which  time  the  red  corpuscles  had  risen  to  4,395,000  in  number 
and  the  white  corpuscles  had  come  down  to  12,500,  of  which 
78.3  per  cent,  were  polynuclears,  7.3  per  cent,  small  lymphocytes 
(no  plasma  cells),  and  14.3  per  cent,  large  monocytes.  The  red 
cells  in  addition  to  their  spectacular  increase  in  number  were 
much  more  normal  in  appearance.  A  good  many  platelets  had 
appeared,  and  free  microblasts,  often  large,  of  which  there  had 
been  none  at  the  earlier  period.  The  polynuclears  were  very 
acidophile  and  granular,  with  full  cytoplasm.  There  was  ex- 
treme progression  to  the  left  in  the  Arneth  sense — that  is  to  say 
a  very  large  number  of  single-nucleated  neutrophiles.  The  large 
monocytes  were  large  and  fairly  typical ;  the  cytoplasm  dark,  but 
clearly  differentiated  from  the  nucleus.  The  number  of  these 
large  monocytes  had  increased,  as  will  be  observed,  by  250  per 
cent.  The  change  in  size  and  quality  was  not  less  conspicuous. 

A  fairly  plausible  interpretation  of  these  microscopical  find- 
ings, and  one  consonant  with  the  clinical  history  and  the  known 
pathology  of  such  cases,  would  be  that  there  was  marked  bac- 
terial infection  (indicated  by  the  leucocytosis,  with  conspicuous 
preponderance  of  polynuclears),  but  that  there  was  also  marked 
general  protein  infection,  comparable  to  the  infection  from  can- 
cer, the  solidified  lung  mass  having  many  of  the  characteristics 
of  a  malignant  neoplasm.  The  response  to  proteal  treatment, 
indicated  by  increase  of  red  corpuscles,  decrease  of  white,  de- 
crease of  the  polynuclear  preponderance,  and  marked  increase  of 
large  monocytes  may  be  taken  as  suggesting  interesting  possi- 
bilities of  proteal  treatment  for  tubercular  cases  even  at  a  late 
stage  of  unfavorable  development. 

In  another  late-stage  case  of  pulmonary  tuberculosis  the  red 
corpuscles  before  the  administration  of  Proteals  numbered  only 
3,964,000,  and  were  of  such  quality  (90  per  cent,  diminutive  and 
misshapen)  that  their  functional  efficiency  must  have  been  far 
more  than  proportionately  reduced.  After  seventeen  days  of 
Proteal  treatment  (doses  of  3  to  7  minims  of  Nos.  37  and  45), 
the  red  cells  were  metamorphosed  in  character,  and  increased  in 
number  to  4,500,000.  Clinically  there  was  striking  improvement. 
Temperature  and  pulse  reduced  to  normal  (from  101  and  115, 
respectively)  ;  cough  much  less ;  better  appetite  and  sleep ; 
strength  and  sense  of  well  being  so  greatly  improved  that  the 
patient  asked  to  be  allowed  to  go  back  to  work.  Prior  to  be- 
ginning treatment  her  physician  had  told  her  that  she  had  but 


THE   SCIENCE   AND  ART   OF   PROTEAL  THERAPY  141 

one  chance  in  a  thousand  to  live,  and  that  chance  conditioned  on 
her  going  at  once  to  the  mountains.  Nine  months  later  this  pa- 
tient seemed  clinically  well,  and  the  blood  record  was :  Haemo- 
globin 85;  red  corpuscles,  5,165,000;  white  corpuscles,  5,500,— 
an  absolutely  satisfactory  numerical  count. 

TUBERCULOSIS  AND  PROTEIN  POISONING 

It  is  my  personal  view  that  an  advanced  case  of  pulmonary 
tuberculosis  represents  a  condition  in  which  the  chief  menace 
is  not  from  toxins  directly  developed  by  the  tubercle  bacillus 
itself,  but  from  toxins  generated  by  mixed  infections  plus  the 
toxic  products  of  partial  proteolysis  of  the  tissues  making  up 
the  lung  mass. 

Stated  otherwise,  I  regard  a  tubercular  mass  as  a  foreign 
growth  which  may  have  the  same  effect  on  the  blood,  the  blood- 
forming  organs,  and  the  organism  at  large  as  the  types  of  foreign 
growths  that  we  term  malignant  neoplasms.  The  tuberculosis 
patient,  like  the  cancer  patient,  dies  ultimately  either  of  hemor- 
rhage or  of  protein  poisoning.  In  the  latter  case  (and  this  may 
be  said  to  represent  the  normal  progress  of  pathological  events, 
if  the  phrase  be  permitted),  the  same  kind  of  strain  is  put  upon 
the  blood-forming  organs,  and  the  same  disturbances  of  the 
blood  cells  are  brought  about  in  tuberculosis  and  in  cancer. 
Clinically,  the  cachexia  of  the  late  stage  tuberculosis  patient 
and  that  of  the  late  stage  cancer  patient  cannot  be  distinguished 
one  from  the  other.  I  have  seen  two  patients  side  by  side,  both 
cachetic  to  the  verge  of  moribundity,  one  having  a  solidified  lung 
and  the  other  a  carcinoma  of  the  stomach,  yet  so  closely  similar 
in  general  appearance  that  even  a  practiced  eye  could  not  deter- 
mine which  patient  had  the  injured  lung  and  which  the  injured 
stomach.  What  could  be  determined  at  a  glance  was  that  both 
patients  manifested  profound  disturbances  of  metabolism,  char- 
acterized by  lack  of  good  red  blood.  Both  of  them  have  blood- 
forming  organs  that  have  overworked  against  persistent  protein 
invasion  until  they  have  reached  the  stage  of  sheer  exhaustion. 

Under  the  microscope,  the  blood  of  these  two  patients  may  be 
as  similar  in  its  abnormalities  (decrease  of  red  corpuscles,  in- 
crease of  white,  preponderance  of  polynuclears,  qualitative  modi- 
fications) as  their  clinical  manifestations  of  malnutrition  are 
similar. 

When  we  consider  the  matter  in  this  light,  it  no  longer  seems 
strange  that  administration  of  the  same  treatment  to  these  two 
patients  may  be  beneficial  to  both.  A  few  drops  of  Proteal  from 
the  same  ampule  may  be  administered  hypodermically  in  succes- 
sion to  the  tubercular  and  cancerous  patients  respectively  day  by 


142      THE   PROTEOMORPHIC   THEORY  AND  THE    NEW    MEDICINE 

day;  and  it  may  fairly  be  asserted  that  each  will  give  evidence, 
both  clinical  and  hematological,  of  an  organic  response  that  is 
definite  and  highly  gratifying. 

As  to  what  will  be  the  ultimate  extent  of  such  response,  no 
predictions  can  be  made  in  any  individual  case.  It  is  axiomatic 
to  say  that  everything  depends  upon  the  degree  of  involvement 
of  tissues,  both  local  and  general ;  the  inherent  vitality  of  the 
patient;  and  the  responsive  capacities  of  the  blood-forming 
mechanism.  These  are  matters  regarding  which  no  two  patients 
will  be  precisely  alike,  and  regarding  which  the  physician  cannot 
always  form  an  accurate  estimate.  In  particular,  that  intangible 
but  highly  important  thing  which  we  call  inherent  vitality  may 
come  to  the  rescue  of  many  a  patient  whose  case  seemed  hope- 
less; whereas  another  patient  whose  state  seemed  less  desperate 
may  not  have  quite  the  same  recuperative  qualities  of  cellular 
tissue.  The  wise  physician  will  always  hold  prognosis  in  abey- 
ance and  watch  for  results  before  forming  an  opinion  in  his  own 
mind  as  to  the  outcome. 

I  would  call  attention  to  what  I  have  said  in  the  cancer 
Monograph  as  to  the  absurdity  of  hoping  to  restore  cells  that 
are  actually  degenerated,  reiterating  that  this  can  no  more  be 
expected  when  these  cells  are  part  of  the  liver  or  pancreas  or 
lung  than  when  they  are  part  of  an  amputated  arm  or  leg. 
But  I  would  also  repeat  that  we  can  seldom  feel  certain  as  to  the 
amount  of  involvement  of  tissue  in  any  given  case  where  an 
internal  organ  is  involved ;  and,  secondly,  that  a  comparatively 
small  portion  of  remaining  normal  tissue  may  sometimes  show 
surprising  capacity  to  take  on  itself  functions  of  the  entire  organ. 
A  familiar  case  illustrating  the  latter  point  is  the  well-known 
capacity  of  one  kidney  to  do  the  work  of  both. 

Questions  of  ultimate  prognosis  aside,  however,  we  are  justi- 
fied by  present  experience  in  expecting  that,  in  a  very  large 
proportion  of  cases  of  the  kind  just  cited  (late  stage  tuberculosis 
and  cancer),  as  well  as  in  a  variety  of  other  conditions  of  dis- 
turbed protein  metabolism  that  have  led  to  anaemic  and  cachetic 
conditions,  the  exhibition  of  Proteals  will  produce  at  least  a 
temporary  response  of  the  blood-forming  organs  that  will  be 
manifested  in  marked  modification  of  the  blood  count  and  in 
more  or  less  conspicuous  clinical  improvement  of  the  patient. 

I  think  I  am  speaking  within  bounds  when  I  say  that  my  ex- 
perience justifies  the  conclusion  that  the  Proteals,  thus  admin- 
istered, have  such  powers  of  stimulating  the  blood-forming 
mechanism  as  to  place  them  in  a  class  quite  by  themselves  among 
tonic  remedies.  I  have  much  confidence  that  the  future  will 
justify  my  present  belief  that  this  form  of  medication  is  destined 


THE   SCIENCE   AND  ART   OF  PROTEAL  THERAPY  143 

to  make  the  old,  familiar  tonic  remedies — notably  iron  and 
arsenic — in  their  old  method  of  administration,  obsolete. 

In  making  this  suggestion,  I  would  not  have  it  understood 
that  I  expect  to  see  iron,  arsenic,  and  other  old  friends  of  this 
category  disappear  at  once  from  the  armamentarium  of  the 
physician.  Proteal  remedies  will  not  altogether  displace  these 
old  friends  any  more  than  salvarsan  has  altogether  displaced 
mercury.  It  is  not  to  be  expected  that  any  one  type  of  medica- 
tion will  be  applicable  to  any  and  every  type  of  case,  even  where 
there  are  seemingly  similar  maladjustments  of  functioning.  Yet 
I  reaffirm  the  conviction  that  present  experience  justifies  the 
belief  that  the  tonic  remedies  that  have  been  almost  the  sole 
reliance  of  the  physician  in  anaemias  associated  with  disturbed 
protein  metabolism  (and  hence  associated  with  most  of  the 
disorders  of  middle  life  and  old  age)  are  rendered  obsolescent 
by  the  advent  of  the  new  method. 

I  am  aware  that  such  an  opinion  must  seem  heretical,  perhaps 
even  fanatical.  Yet  I  express  and  reaffirm  it  calmly  and  with 
confidence  based  on  the  observation  of  a  series  of  cases  large 
enough,  and  varied  enough,  in  my  opinion,  to  be  dependable. 

It  will  be  understood  that  the  opinion  just  expressed  is  based 
on  personal,  first-hand  observation  both  clinical  and  microscopi- 
cal. The  work  with  which  we  are  dealing  is  pioneer  work.  So 
far  as  I  am  aware,  no  one  but  myself  and  my  immediate  asso- 
ciates have  hitherto  dealt  extensively  with  non-specific  vegetable 
proteins  as  such,  either  in  laboratory  or  clinic,  as  therapeutic 
agents  for  hypodermic  administration.  It  is  true  that  several 
thousand  physicians  have  administered  the  original  proteal  ex- 
tract, and  I  have  profited  by  their  clinical  experience;  but  for 
the  most  part  the  physicians  have  administered  the  remedy  em- 
pirically in  accordance  with  my  directions,  and  comparatively 
few  of  them  have  watched  the  blood  count.  Those  who  have 
done  so,  however,  have  reported  observations,  confirming  in  the 
most  substantial  manner  the  original  studies  with  which  the 
present  volume  is  largely  concerned. 

Here,  for  example,  is  a  letter  that  chances  to  come  to  hand  the 
morning  of  the  present  writing,  from  a  prominent  physician  in 
a  neighboring  city  who  says ; 

"I  have  now  used  the  Proteal  No.  37  for  twelve  days  and  have 
reached  the  dose  of  15  minims  without  any  local  or  general  reac- 
tion. I  have  increased  the  dose  to  17  minims  and  will  of  course 
watch  for  reaction.  The  only  constitutional  change  thus  far  has 
been  a  true  increase  in  the  mononuclear  leucocytes  with  a  de- 
crease of  the  small  lymphocytes ;  also  an  increase  in  the  red  blood 
cell  count." 


144      THE    PROTEOMORPHIC   THEORY   AND   THE    NEW    MEDICINE 

A  pioneer  in  any  line  of  research  work  must  always  await  with 
interest  corroboration  of  his  results  by  other  workers.  Naturally 
I  shall  be  pleased  to  have  reports  at  all  times  from  candid  ob- 
servers, whether  by  way  of  corroboration  or  criticism ;  but  I 
repeat  that  the  evidence  already  in  hand,  based  on  my  personal 
observation,  is  so  comprehensive,  so  unequivocal,  and  so  con- 
vincing that  I  await  the  ultimate  verdict  of  the  profession  with 
absolute  confidence. 

All  this,  however,  is  in  effect  a  digression.  Let  us  again  take 
up  briefly  the  interpretation  of  the  blood  changes  that  are  brought 
about  by  Proteal  medication,  in  so  far  as  they  are  of  practical 
interest  and  importance  to  the  practitioner ;  following  with  some 
explicit  hints  as  to  the  practical  administration  of  the  new  method 
in  cases  of  malnutrition  of  sundry  types,  from  simple  anaemias 
to  the  profound  cachexia  of  tuberculosis  and  carcinoma. 

AN  INTERPRETATION  OF  CORPUSCULAR  ACTION 

As  regards  a  somewhat  more  detailed  interpretation  of  the 
blood  count,  and  in  particular  the  differential  count,  there  are 
certain  opinions  that  I  hold  provisionally,  regarding  which  more 
elaborate  publication  will  be  made  elsewhere,  to  which  brief 
attention  may  be  given.  As  elsewhere  pointed  out,  this  subject 
is  one  in  which  very  little  work  has  been  done,  and  regarding 
which  the  opinions  of  the  pathologists  are  altogether  vague.  So 
far  as  I  know,  the  question  has  not  hitherto  been  asked,  let  alone 
answered,  as  to  why  in  normal  blood  the  polynuclears  number 
60  to  70  per  cent,  of  the  total  leucocytes,  the  lymphocytes  20  to 
25  per  cent.,  and  the  large  monocytes  and  eosinophiles  and  baso- 
philes  make  up  a  relatively  insignificant  population.  Yet  there 
must  be  reasons  why  there  is  this  distribution  of  corpuscles  in 
normal  blood;  reasons  associated  with  the  variant  functions  of 
the  different  types  of  cells. 

In  attempting  to  interpret  the  observed  blood  changes  under 
Proteal  treatment,  peculiar  difficulties  are  encountered  in  the 
fact  that  the  physiological  activities  of  the  corpuscles  have  been 
but  vaguely  understood. 

Ordinarily,  the  pathologist  is  guided  in  the  interpretation  of 
what  he  sees  by  known  physiological  laws.  The  student  of 
microscopic  pathology  has  for  guide  the  well-recognized  findings 
of  the  histologist.  But  in  the  present  instance  such  aid  is  not 
available.  We  have,  to  be  sure,  records  as  to  the  relative  num- 
bers of  different  types  of.  blood  corpuscles  in  health  and  acute 
infections.  The  further  fact  is  available  that  the  polynuclears 
appear  to  be  especially  concerned  in  the  direct  battle  against  in- 
vading bacteria.  But  with  that  antecedent  knowledge  practi- 


THE    SCIENCE    AND   ART   OF   PROTEAL   THERAPY  145 

cally  ends.  If  one  asks,  for  example,  why  basophiles,  eosino- 
philes,  and  large  monocytes  are  few,  whereas  small  lymphocytes 
are  relatively  numerous,  and  polynuclears  still  more  so,  no  an- 
swer has  hitherto  been  forthcoming. 

It  is  axiomatic  to  say  that  such  distribution  of  numbers  must 
be  consonant  with  the  needs  of  the  average  body  and  with  specific 
functions  of  the  different  types  of  leucocytes;  but  as  to  the 
nature  of  these  needs  and  the  character  of  the  function  there  is 
entire  silence  on  the  part  of  physiologists  and  pathologists  alike. 

In  the  first  exposition  of  the  Proteomorphic  theory,  I  put 
forward  the  suggestion  that  the  leucocytes  as  a  class  have  for 
their  broad  general  function  the  hydrolysis  of  proteins  and  the 
earlier  products  of  protein  decompounding.  To  the  mononuclear 
cells  in  particular  I  ascribed  the  function  of  dealing  with  the 
full-sized  protein  molecule.  It  was  further  noted  that  the  large 
monocytes  appear  to  have  a  peculiar  relation  to  the  decom- 
pounding of  such  neoplastic  cells  as  those  of  cancer,  and  I  ven- 
tured the  suggestion  that  the  small  lymphocyte  has  to  do  with 
the  catabolism  of  normal  serum  proteins,  in  rendering  them 
available  for  bodily  use.  But  beyond  this  no  detailed  interpreta- 
tion of  the  functions  of  the  different  leucocytes  was  attempted. 

In  the  three  and  a  half  years  that  have  elapsed  since  the  Pro- 
teomorphic theory  was  conceived  and  exposited,  I  have  devoted 
a  large  share  of  my  time  to  studies  that  brought  me  directly  in 
contact  with  problems  of  corpuscular  activity  in  disease  and  in 
health.  During  a  considerable  part  of  this  time  I  have  devoted 
several  hours  of  each  day  to  the  microscopic  study  of  blood 
corpuscles  in  counting-chamber  and  on  stained  smear.  While 
chiefly  concerned  with  the  blood  of  persons  suffering  from 
maladies  of  disturbed  metabolism,  and  in  particular  with  modi- 
fications of  blood  under  protein  treatment,  I  have  checked  these 
observations  with  studies  of  normal  blood  under  various  condi- 
tions. 

This  is  not  the  place  to  give  detailed  account  of  these  studies, 
which,  indeed,  have  not  yet  reached  the  stage  where  final  an- 
alysis is  desirable.  But,  by  way  of  preliminary  report  of  matters 
hitherto  unpublished,  it  may  be  worth  while  to  give  a  brief  out- 
line of  a  theory  of  corpuscular  action  that  seems  to  be  at  least 
worth  considering  as  a  working  hypothesis,  although  confessedly 
subject  to  modification  in  the  light  of  future  evidence.  This 
hypothesis  is  only  one  of  numerous  suggestions  that  present 
themselves,  and  which  at  various  times  have  been  entertained  in 
the  course  of  my  investigation.  I  hold  it  and  put  it  forward 
not  in  the  least  dogmatically  or  as  having  finality,  but  in  the 
thought  that  it  may  serve  a  useful  purpose  in  guiding  the  inves- 
tigations of  others,— and  I  assume  that  the  present  publication, 


146     THE   PROTEOMORPHIC  THEORY  AND  THE   NEW   MEDICINE 

because  of  the  hematological  facts  already  presented,  will  stim- 
ulate a  large  number  of  investigators  to  take  up  the  study  of 
the  blood  with  new  zest  and  from  new  angles. 

The  working  hypothesis  which  I  now  suggest  hinges  on  an 
assumption  that  is  almost  absurdly  simple — which  may  or  may 
not  be  a  merit.  The  suggestion  is  this — that  the  different  groups 
of  leucocytes,  in  the  order  of  their  numerical  abundance,  deal 
primarily  with  the  successive  groups  of  protein  decomposition 
products  in  the  order  of  their  numerical  molecular  representa- 
tion. That  is  to  say,  the  least  abundant  group  of  leucocytes 
(namely  the  large  mononuclears  and  binuclears)  deal  with 
full-sized  protein  molecules ;  the  next  larger  group  of  leucocytes 
(namely  the  small  lymphocytes)  deal  with  molecules  of  the  pro- 
teose  or  albuminose  order ;  the  third  and  most  abundant  group 
of  leucocytes  (namely  the  polynuclears  or  neutrophiles)  deal- 
ing with  protein-product  molecules  of  the  peptone  order; — it 
being  understood  that  the  extremely  abundant  red  corpuscles 
take  up  the  work  of  decompounding  at  the  polypeptid  stage  and 
complete  the  final  disintegration  into  amino  acids  and  toxic  by- 
products, such  as  uric  acid,  urea,  and  creatinine. 

It  will  be  recalled,  as  giving  a  sort  of  apriori  plausibility  to 
the  assumption,  that  the  numerical  relations  between  the  normal 
numbers  of  different  types  of  leucocytes  are,  in  general  terms, 
the  same  as  the  numerical  relations  between  the  numbers  of 
molecules  in  the  different  orders  of  protein  products.  This 
relation  of  course  does  not  hold  when  the  red  corpuscles  are 
under  consideration,  since  these  are  many  times  more  numerous. 
But  this  seeming  inconsistency  is  explicable  on  the  plausible  as- 
sumption that  large  quantities  of  molecules  of  the  polypeptid 
order  enter  the  circulation  normally,  through  the  intestinal  wall. 
Indeed,  it  has  been  suggested  that  the  red  corpuscles  may  be 
called  upon  under  normal  conditions  to  complete  the  hydrolysis 
of  the  polypeptids  wholly  or  in  part,  the  question  as  to  the  pre- 
cise condition  in  which  the  protein  product  normally  enters  the 
circulation  not  being  clearly  settled. 

Even  though  the  enteric  enzymes  normally  reduce  the  poly- 
peptids to  the  amino-acid  stage,  it  must  happen  very  generally 
that  they  fail  to  some  extent  of  their  complete  function,  per- 
mitting the  entrance  of  a  greater  or  less  number  of  polypeptid 
molecules.  The  same  thing  is  true,  of  course,  of  a  certain  num- 
ber of  large  molecules,  including  the  full-sized  protein  molecule 
itself;  but  the  entrance  of  the  latter  must  be  relatively  infre- 
quent,—  a  fact  that  in  itself  accounts,  we  may  suppose,  for  the 
relative  paucity  of  large  mononuclears  in  normal  blood. 

It  will  be  observed  that  in  the  above  summary,  reference  is 
made  to  a  group  comprising  mononuclears  and  binuclears.  The 


THE   SCIENCE   AND  ART  OF  PROTEAL  THERAPY  147 

latter  term  of  course  connotes  eosinophiles  and  basophiles. 
Very  little  has  been  said  in  recent  pages  about  these  two  types 
of  leucocytes,  beyond  noting  that  they  tend  to  increase  under 
proteal  treatment  just  as  do  the  large  monocytes.  I  have  long 
been  disposed  to  regard  the  eosinophiles  and  basophiles  as  cells 
of  the  same  order,  representing  either  stages  of  individual  de- 
velopment or  modified  condition  of  chemical  composition  (say 
acidity  versus  alkalinity),  in  effect  no  more  variant  than  different 
specimens  of  polynuclear  leucocytes  some  of  which  show  clear 
unstained  cytoplasm  while  others  are  markedly  granular  and 
acidophile. 

I  am  by  no  means  certain  that  basophiles  and  eosinophiles  are 
not  to  be  regarded  as  matured  stages  of  large  monocyte  devel- 
opment. It  is  at  least  within  the  possibility  that  a  monocyte  that 
has  ingested  a  certain  amount  of  protein  and  transformed  it,  let 
us  say,  into  proteose  may  divide  its  nucleus  and  have  its  enlarged 
cytoplasm  just  prior  to  disruption  assume  a  condition  that  mod- 
ifies its  staining  qualities  so  that  its  appearance  is  greatly  modi- 
fied. On  this  assumption,  the  relative  scarcity  of  eosinophiles 
and  basophiles  would  be  explicable  on  the  ground  of  their  relative 
shortness  of  individual  life,  it  being  assumed  that  the  incidence 
of  the  granular  condition  presages  disruption. 

It  may  be  recalled  in  this  connection  that  the  Russian  inves- 
tigators Avrowrow  and  Timofeeosky  have  suggested  that  eosino- 
philes are  only  monocytes  that  have  ingested  red  blood  cor- 
puscles. 

No  doubt  many  objections  could  be  urged  against  this  linking 
of  the  large  monocyte  and  the  eosinophile  and  basophile  as  mem- 
bers of  the  same  series.  I  am  not  aware,  however,  of  any  ob- 
jection that  seems  insuperable.  Meantime  the  observed  coin- 
cidence between  increase  of  large  monocytes  and  increase  of 
eosinophile  and  basophiles  under  proteal  treatment  (see  numer- 
ous tables  in  the  Monograph),  is  at  least  not  inconsistent  with 
the  assumption. 

It  is  consonant  with  what  we  know  of  the  mutual  relations 
of  bodily  organs  to  assume  that,  even  if  the  above  interpretation 
of  the  primary  action  of  different  types  of  leucocytes  be  ac- 
cepted, it  does  not  follow  that  any  type  of  leucocyte  is  abso- 
lutely restricted  in  its  possible  activities  to  the  hydrolyzing  of 
protein  products  of  a  particular  size.  I  have  already  suggested 
that  the  stage  of  decompounding  to  which  a  protein  molecule 
may  be  subjected  within  the  leucocyte  may  depend  to  some  ex- 
tent on  the  amount  of  pabulum  ingested,  which  in  turn  would  be 
a  function  of  the  abundance  of  leucocytes  on  one  hand  and  of 
protein  products  in  the  blood  on  the  other. 

To  illustrate  my  meaning,  we  might  assume  that,  granted  a 


148      THE   PROTEOMORPHIC  THEORY  AND  THE   NEW    MEDICINE 

given  prevalence  of  full-sized  protein  molecules,  when  the  large 
mononuclears  are  few,  they  would  individually  secure  large  in- 
crements of  pabulum,  and  would  on  the  average  be  disrupted 
when  this  pabulum  has  reached  the  proteose  stage,  thus  necessi- 
tating a  full  equipment  of  small  lymphocytes  to  take  up  the  work 
of  hydrolyses.  On  the  other  hand,  if  without  increase  of  pro- 
tein pabulum,  the  number  of  large  monocytes  is  increased,  we 
may  assume  that  on  the  average  they  would  carry  the  work  of 
decompounding  to  a  lower  stage,  possibly  even  to  the  peptone 
stage,  and  hence  be  able  to  turn  their  product  over  directly  to  the 
neutrophiles,  thus  to  some  extent  rendering  the  presence  of  small 
lymphocytes  superfluous.  Some  blood  charts  have  been  pre- 
sented which  seem  to  give  plausibility  to  this  suggested  com- 
plementary relation  between  the  activities  of  the  large  and  small 
monocytes. 

Applying  the  same  line  of  reasoning  to  other  types  of  leuco- 
cytes, we  may  assume  that  under  exceptional  circumstances,  the 
small  lymphocyte  may  be  able  to  deal  with  the  full-sized  protein 
molecule  on  one  hand  and  to  bring  it  to  something  approaching 
the  polypeptid  stage  on  the  other  hand ;  thus  supplementing  the 
functions  of  large  monocytes  and  of  polynuclears.  Cases  of 
lymphatic  leukaemia  suggest  this  possibility.  Meantime  the  poly- 
nuclear  itself,  although  ordinarily  concerned  with  transforming 
peptones  into  polypeptids  may  conceivably  on  occasion  deal  with 
proteose  on  one  hand  and  carry  the  polypeptids  toward  the  amino- 
acid  stage  on  the  other.  A  certain  complementary  relation  ob- 
servable between  the  mononuclears,  as  a  group,  and  the  poly- 
nuclears, in  the  charts  before  referred  to,  may  perhaps  thus  be 
explained.  That  a  full  red-cell  equipment  minimizes  to  some 
extent  the  need  of  the  services  of  polynuclears  is  also  at  least  a 
tenable  hypothesis. 

I  have  under  treatment  a  patient  who  for  months  has  main- 
tained a  clinical  status  of  fairly  robust  health  with  a  red-cell 
equipment  of  from  2,176,000  to  3,909,000,  and  a  leucocyte  count 
(chiefly  small  lymphocytes)  ranging  from  680,000  to  1,412,000. 
On  the  smear,  the  small  lymphocytes  are  like  bunches  of  grapes ; 
large  mononuclears  with  obscure  nuclei  are  abundant ;  but  poly- 
nuclears are  hard  to  find.  Here  it  is  impossible  to  avoid  the 
inference  that  the  small  lymphocytes  perform  functions  normally 
reserved  for  polynuclears  on  one  hand  and  erythrocytes  on  the 
other.  This  interesting  case  of  lymphatic  leuksemia  will  be  dis- 
cussed in  greater  detail  elsewhere. 

It  is  probable  that  another  factor  that  may  disturb  the  mutual 
relations  of  the  white  corpuscles  is  to  be  found  in  the  relative 
amount  of  fat  to  be  dealt  with  in  any  organism.  I  have  sug- 
gested that  the  polynuclears  may  have  a  share  in  dealing  with 


THE   SCIENCE   AND   ART  OF   PROTEAL  THERAPY  149 

the  metamorphosis  of  fats ;  but  it  is  consistent  with  the  above  line 
of  reasoning  to  assume  that  the  lymphocytes  also  may  have  a 
hand  in  this  work.  Possibly  the  relative  shares  of  the  two 
types  of  leucocytes  in  dealing  with  fats  may  vary  indefinitely 
under  diversified  conditions. 

A  further  word  must  be  said  about  the  relation  of  the  various 
leucocytes  to  the  type  of  protein  represented  in  the  bodies  of 
bacteria.  At  first  glance  it  may  seem  that  the  observed  fact  that 
polynuclears  deal  with  bacteria,  ingesting  them  bodily,  is  incon- 
sistent with  the  assumption  that  the  chief  work  of  the  polynu- 
clears is  to  deal  with  the  partially  decompounded  protein  mole- 
cule. As  to  this,  however,  it  will  be  recalled  that  the  suggestion 
was  made  that  the  so-called  "opsonins,"  the  presence  of  which 
was  found  by  Wright  to  determine  the  activities  of  the  leuco- 
cytes as  ingesters  of  bacteria,  may  be  enzymes  secreted  by  the 
mononuclear  leucocytes ;  but  it  is  perhaps  even  more  important 
to  recall  that  the  proteins  of  bacteria  are  probably  very  different 
in  quality  from  the  proteins  of  vegetable  and  animal  tissues  in 
general. 

Reference  has  already  been  made  to  the  fact  that  the  encase- 
ment of  the  bacteria  is  of  a  fatty  or  lipoid  character.  It  has 
been  pointed  out  by  Leathes  that  it  is  not  the  cell-membrane 
alone  of  the  bacteria  that  is  so  constituted,  but  that  the  fats  enter 
into  its  entire  structure.  He  says:  "These  fatty  substances, 
which  form  a  considerable  part  of  the  bodies  of  tubercle  bacilli, 
not  only  exhibit  a  very  low  iodine  value,  but  offer  remarkable 
resistance  to  measures  that  are  commonly  efficacious  in  saponi- 
fying fats.  And  there  are  reasons  for  thinking  that  the  vitality 
and  power  of  resistance  of  such  organisms  is  intimately  de- 
pendent upon  the  properties  of  the  fat  in  which  their  bodies  are 
enclosed  or  with  which  they  are  impregnated." 

In  dealing  with  the  bodies  of  pathogenic  bacteria,  then,  the 
organism  is  not  contending  at  all  exclusively  with  foreign  pro- 
teins, but  with  structures  in  which  the  protein  basis  is  so  in- 
corporated with  fatty  matter  as  to  modify  the  conditions  very 
markedly.  Moreover,  it  is  probable  that  the  bacterial  protein 
itself  is  of  a  quite  different  order  from  the  proteins  of  true 
plants  and  of  animals.  The  low  plane  occupied  by  bacteria  in 
the  organic  scale  suggests  the  probability  that  the  bacterial  pro- 
teins have  molecules  of  a  relatively  simple  order,  comparable 
perhaps  in  their  complexity  to  peptones  or  proteoses  rather  than 
to  true  proteins.  On  this  assumption,  as  well  as  in  consideration 
of  the  presence  of  the  fat,  the  recognized  capacity  of  the  poly- 
nuclears to  deal  v;ith  bacteria  is  entirely  consistent  with  the 
function  ascribed  to  these  leucocytes  in  the  above  provisional 
hypothesis.  The  instances  of  observed  incapacity  of  the  large 


150     THE  PROTEOMORPHIC  THEORY  AND  THE   NEW   MEDICINE 

monocytes  to  deal  with  bacteria  find  further  explanation  in  the 
assumption  that  the  bacterial  proteins  are  of  a  low  order  of 
molecule  structure. 

Incidentally,  this  line  of  reasoning  makes  it  clear  that  we 
are  not  to  expect  the  same  increase  in  large  monocytes  from  the 
use  of  bacterial  proteins  as  proteantigens  that  may  be  expected 
from  the  use  of  vegetable  or  animal  proteins.  The  observed 
polynucleosis  from  the  injection  of  bacterial  products  is  quite 
what  might  be  expected. 

It  may  be  added  that  if  the  above  hypothesis  is  valid  as  to  the 
assumption  that  the  large  monocyte  is  chiefly  concerned  with 
the  full-sized  protein  molecule,  we  should  not  expect  so  pro- 
nounced a  large  monocytosis  from  the  injection  of,  for  example, 
peptones  as  from  the  use  of  the  full-sized  protein  molecUie  or 
molecules  of  the  proteose  order.  Practical  observation  of  the 
relative  response  to  proteins,  proteoses,  and  peptones,  used  as 
antigens,  when  carried  out  on  an  adequate  scale,  will  go  far 
toward  testing  the  validity  of  the  above  assumption  as  to  the 
specific  functions  of  different  types  of  leucocytes.  Experiments 
directed  toward  this  end  are  already  under  way.  Comparative 
studies  are  being  made,  for  example,  of  blood  charts  in  cases 
treated  with  the  unbroken  protein  molecule  as  compared  with 
cases  treated  with  the  newer  Proteals,  containing  proteoses  and 
peptones. 

A  tentative  analysis  of  these  tables  tends  to  give  a  certain 
amount  of  support  to  the  above  thesis,  inasmuch  as  the  re- 
sponse to  the  partially  hydrolyzed  proteins  appears  to  include 
the  polynuclears  more  markedly  and  the  eosinophiles  and  bas- 
ophiles  less  markedly  than  the  response  to  the  unbroken  mole- 
cule. The  evidence,  however,  is  not  yet  sufficiently  extensive 
to  be  demonstrative,  as  only  a  small  part  of  the  material  in  hand 
has  been  analyzed.  Pending  the  results  of  such  analysis,  it  will 
be  well  to  bear  in  mind  the  fact  that  the  generalization  as  to  the 
protein  blood  response  enunciated  in  the  first  edition  of  the  can- 
cer Monograph  and  throughout  the  earlier  chapters  of  this  book 
refer  to  the  unbroken  protein  molecule. 

Meantime  the  series  of  tables  and  charts  already  in  hand, 
showing  the  corpuscular  response  to  the  administration  of  pro- 
teantigens for  the  most  part  representing  the  full-sized  molecule, 
appear  to  establish  the  broader  outlines  of  the  Proteomorphic 
theory  as  to  the  manner  of  handling  of  foreign  proteins  in  the 
parenteral  system  beyond  cavil.  No  one  who  studies  these  tables 
even  casually  is  likely  to  question,  I  take  it,  that  the  prote- 
antigen  response  is  directly  and  strikingly  concerned  with  the 
blood-forming  organs,  and  that  increase  of  large  mononuclear 


THE   SCIENCE  AND  ART  OF  PROTEAL  THERAPY  151 

leucocytes  on  one  hand  and  of  red  corpuscles  on  the  other  are 
critical  features  of  that  response. 

That  the  characteristic  response  may  be  kept  up  for  many 
months  is  adequately  demonstrated  in  tables  above  presented. 
The  efficacy  of  substituting  new  proteins  when  the  systemic  re- 
sponse has  flagged  has  been  amply  proved.  Whether  there  are 
any  limits  to  such  substitution,  and  to  what  extent  it  is  desir- 
able to  keep  up  the  proteantigen  treatment  after  the  seeming 
recovery  of  a  patient,  are  questions  for  the  future  to  decide.  It 
would  appear  that  the  study  of  the  blood  in  a  large  series  of 
cases  must  furnish  the  best  clues  to  an  answer. 


AGE  AND  THE  BLOOD  COUNT 

In  attempting  to  account  for  the  observed  facts  of  corpuscular 
variation  between  childhood  and  adult  life,  I  have  been  led  to 
question  whether  the  salient  fact  that  the  polynuclear  count 
increases  from  about  40  to  60  or  70  per  cent,  of  the  total  leuco- 
cyte count  with  the  advance  in  years  from  adolescence  to  adult 
life,  may  not  be  merely  an  evidence  of  response  on  the  part  of 
the  organism  to  the  perpetual  bacterial  bombardment  to  which  it 
is  subjected.  It  is  familiarly  known  that  bacterial  products 
make  up  a  significant  part  of  the  normal  faeces ;  and,  in  general, 
it  is  understood  that  we  are  perpetually  assailed  by  bacteria 
which  have  become  relatively  innocuous  merely  because  of  their 
universal  prevalence. 

Obviously,  in  the  natural  course  of  events,  such  infection  must 
become  cumulative;  that  is  to  say,  we  must  suppose  that  on 
the  average  the  adult  individual  is  more  comprehensively  affected 
than  the  average  child.  On  the  hypothesis  put  forward  in  an 
earlier  section,  it  would  be  the  middle  products  of  protein  de- 
compounding chiefly  in  excess.  Conceivably  this  may  be  the 
reason  why  the  polynuclear  count  goes  up,  reaching  in  adult  life 
very  frequently  a  status  of  approximately  double  that  of  the 
average  of  childhood  and  adolescence. 

If  this  interpretation  be  correct,  the  so-called  normal  leuco- 
cyte count  of  adult  life  might  be  said  to  be  in  itself  a  mani- 
festation of  abnormality.  Such  a  statement  sounds  paradoxical, 
but  it  may  connote  an  important  truth.  It  is  a  suggestive  fact 
that  in  a  patient  long  subjected  to  Proteal  treatment  associated 
with  careful  attention  to  hygiene  of  diet  and  digestion,  it  is 
observed  that  the  polynuclear  count  very  generally  comes  down 
as  the  patient  improves,  and  may  even  be  reduced  to  the  stand- 
ard of  childhood — 40  per  cent,  or  thereabouts.  In  two  or  three 
instances  where  the  patient  had  been  for  many  months  under 


152      THE   PROTEOMORPHIC   THEORY   AND  THE   NEW    MEDICINE 

proteal  treatment,  I  have  recorded  a  poly  nuclear  count  of  only 
39  per  cent. 

It  seems  not  altogether  unlikely  that  the  relatively  low  poly- 
nuclear  count  of  childhood  accounts  for  the  susceptibility  of 
the  child  to  the  familiar  exanthemata;  and  that,  contrariwise, 
the  abundance  of  polynuclears  in  the  adult  organism  accounts  for 
the  relative  immunity  of  adults  to  these  diseases.  It  would  appear 
to  be  a  case  where  the  righting  equipment  of  the  body,  as  directed 
against  bacteria  in  general,  has  been  brought  to  a  stage  of  pre- 
paredness in  the  average  adult  that  makes  it  possible  to  attack 
and  overwhelm  the  germs  of,  for  example,  measles  and  whoop- 
ing cough,  whereas  the  same  germs  would  have  been  able  to 
make  effective  entry  into  the  system  of  the  average  child. 

A  similar  line  of  reasoning  may  perhaps  be  applied  tc  Account 
for  the  observed  fact  that  the  red  corpuscles  are  less  abundant 
in  the  blood  of  the  child  and  adolescence  than  in  the  blood  of 
the  average  adult.  Incidentally,  this  fact  in  itself  would  appear 
to  prove  that  the  red  corpuscles  have  some  function  other  than 
the  carrying  of  oxygen,  inasmuch  as  the  cellular  activities  of 
childhood  and  adolescence  must  certainly  be  somewhat  more  than 
on  a  par  with  those  of  the  adult.  Accepting  the  Proteomorphic 
interpretation  of  the  function  of  the  red  corpuscles  as  the  agents 
concerned  in  dealing  with  the  end  products  of  protein  metabol- 
ism, the  increase  of  these  corpuscles  in  adult  life  might  be 
interpreted  as  showing  an  increased  protein  infection  of  a  char- 
acter to  charge  the  blood  with  larger  quantities  of  end  products 
(of  the  polypeptid  order)  with  advancing  years,  associated  per- 
haps with  waning  power  of  the  digestive  apparatus. 

The  fact  that  physiologists  commonly  mention  4,500,000  red 
corpuscles  as  the  average  normal  increment  for  women  and 
5,000,000  as  the  increment  for  men — a  fact  hitherto,  so  far  as  I 
know,  entirely  unexplained — may  conceivably  be  accounted  for 
on  the  supposition  that  men,  on  the  average,  eat  larger  quanti- 
ties of  protein  food  than  women.  The  proverbially  daintier  appe- 
tites of  the  female  sex  accord  with  this  hypothesis ;  which  is  here 
put  forward,  however,  only  as  a  suggestion.  The  greater  activ- 
ity of  the  male  would  be  an  obvious  explanation  from  a  more 
conventional  angle ;  but  comparative  histology  robs  this  explana- 
tion of  force  by  reminding  us  that  relatively  inactive  animals  like 
the  sheep  have  a  high  erythrocyte  count,  whereas  excessively 
active  birds  have  a  low  count. 

Meantime  my  personal  studies  leave  me  very  much  in  doubt 
as  to  whether  there  is,  in  point  of  fact,  an  established  sex  factor 
in  determining  the  red  cell  count — an  item  of  obvious  prelim- 
inary importance,  deserving  further  investigation. 

Whatever  the  fact  as  to  sex  differences,  however,  it  appears 


THE   SCIENCE   AND   ART   OF   PROTEAL  THERAPY  153 

to  be  fairly  established  that  the  lymphocyte  population  of  the 
child's  blood,  and  in  particular  the  large  monocyte  population, 
decreases  with  advancing  age.  This  would  seem  to  suggest 
(holding  still  to  the  Proteomorphic  interpretation)  that  the  adult 
organism  is  in  general  called  upon  to  deal  less  comprehensively 
with  the  full-sized  foreign  protein  molecule  than  is  the  organism 
of  the  child.  A  plausible  explanation  of  this,  as  already  sug- 
gested, may  be  found  in  the  obvious  needs  of  the  growing  organ- 
ism, where  nitrogenous  tissue  is  being  built  up  day  by  day;  as 
contrasted  with  the  adult  organism,  where  the  nitrogenous  tissues 
are  only  holding  their  own,  or  are  actually  degenerating. 

Incidentally,  it  may  be  supposed  that  the  normally  large  equip- 
ment of  mononuclear  cells  in  the  blood  of  the  child  and  adolescent 
may  account  in  some  measure  for  the  relative  immunity  to  the 
growth  of  malignant  neoplasms  in  early  life.  Contrariwise,  the 
susceptibility  of  old  age  to  the  growth  of  such  neoplasms  may 
be  associated  with  the  decreased  numbers,  and,  presumably,  de- 
creased functional  activities  of  the  mononuclear  leucocytes  chiefly 
concerned  in  handling  unbroken  proteins  in  general  and  .lawless 
neoplastic  cells  in  particular. 

FURTHER  HINTS  AS  TO  DIFFERENTIAL  FUNCTIONS 

Such  a  suggestion  is  obviously  consonant  with  the  interpreta- 
tion of  the  role  of  the  lymphocyte  and  the  large  mononuclears 
put  forward  in  connection  with  the  Proteomorphic  theory,  and 
constantly  reiterated  in  the  present  volume.  It  must  be  freely 
admitted,  however,  that  our  knowledge  of  the  subject  is  at  best 
fragmentary,  and  that  a  great  deal  more  work  must  be  done 
before  we  can  hope  for  definite  answers  to  many  questions  that 
obtrude  themselves  whenever  one  considers  a  blood  smear  with 
philosophical — that  is  to  say,  with  childlike — inquisitiveness. 

As  provisional  deductions  from  my  own  personal  studies,  I 
have  suggested  the  possibility  that  one  chief  role  of  the  poly- 
nuclear  leucocytes  may  have  to  do  with  the  metabolism  of  fats. 
Observation  has  taught  me  to  expect  to  find  a  relative  and  abso- 
lute leucopcenia  in  examining  the  blood  of  obese  patients  of  the 
anaemic  type.  It  has  just  been  remarked  that  bacteria  are  sur- 
rounded by  a  lipoid  covering  and  have  a  body  structure  that 
incorporates  lipoids.  It  is  familiarly  known  also  that  the  poly- 
nuclear  has  to  do  with  the  fight  against  bacteria — that  being  a 
classical  observation  of  Metchnikoff  that  has  hitherto  stood  al- 
most alone  as  an  interpretation  of  specific  functions  of  a  par- 
ticular type  of  leucocyte.  It  is  not  improbable  that  lipoids  also 
enter  into  the  constitution  of  the  cell  membrane  of  the  cells  of 
the  normal  organism,  and  of  such  modifications  of  these  cells 


154      THE   PROTEOMORPHIC  THEORY   AND  THE    NEW    MEDICINE 

as  go  to  make  up  the  tissues  of  malignant  neoplasms.  If  such 
is  the  case,  and  if  the  enzymes  of  the  polynuclears  have  an  im- 
portant share  in  the  digestion  of  fats,  it  may  plausibly  be  assumed 
that  the  polynuclears  have  an  important  share  in  attacking  the 
cancer  cells,  thus  co-operating  with  the  mononuclears.  Reference 
was  made  to  this  possibility  in  the  Monograph,  in  connection 
with  the  observation  that  partially  degenerated  polynuclears  are 
observed  to  congregate,  along  with  the  mononuclears,  in  the 
region  of  a  neoplasm  that  is  undergoing  disintegration. 

It  has  been  observed  that  large  mononuclear  leucocytes  on 
occasion  ingest  bacteria  and  yet  are  unable  to  digest  them.  This 
may  be  because  the  monocyte  does  not  produce  an  enzyme  that 
attacks  the  fatty  substances,  and  hence  is  unable  to  penetrate  the 
cell  wall  of  the  bacterium.  This  initial  stage  of  combating  the 
bacterium  being  reserved  for  the  polynuclear,  and  this  function 
having  been  accomplished,  the  protein  content  of  the  bacterium, 
whatever  its  molecular  status,  may  be  turned  over  to  the  mono- 
cytes  for  further  proteolysis,  the  ultimate  product  being  handed 
on  to  the  red  corpuscle,  according  to  the  hypothesis  of  the  Pro- 
teomorphic  theory. 

It  is  a  familiar  observation  that  a  preponderant  number  of  the 
leucocytes  that  spring  into  being  when  there  is  a  marked  bac- 
terial infection  are  polynuclear  in  character.  This  is  consistent 
with  the  above  supposition  that  the  activities  of  this  particular 
type  of  leucocytes  are  necessary  to  begin  the  destruction  of  the 
bacterium.  It  has  been  further  observed,  however,  that  at  a 
later  stage  of  infection  there  may  be  a  relative  and  absolute 
lymphocytosis.  This  is  at  least  consistent  with  the  supposition 
that  the  mononuclear  leucocytes  handle  the  bacterial  proteins 
after  the  polynuclears  have  made  their  protein  contents  available 
by  dissolving  the  lipoid  membrane. 

By  way  of  recapitulation,  and  condensed  summary,  it  may  be 
recalled  that  under  normal  conditions,  according  to  the  provi- 
sional hypothesis  on  which  I  am  working,  the  polynuclears  are 
concerned  with  the  handling  of  the  fats  normally  in  the  blood, 
which  somewhat  exceed  in  amount,  it  may  be  observed,  the 
foreign  proteins  normally  present  there.  The  handling  of  this 
normal  fat,  plus  the  handling  of  the  bacteria  that  make  perpetual 
onslaught,  may  account  for  the  organic  necessity  of  having  the 
neutrophile  population  of  the  blood  about  three  times  as  great 
as  the  mononuclear  population.  The  relative  paucity  of  the 
mononuclears,  and  in  particular  of  the  large  monocytes,  may 
perhaps  be  provisionally  accounted  for  as  explained  by  the  pau- 
city of  unbroken  foreign  proteins  in  normal  blood.  In  childhood, 
when  these  proteins  are  abundant,  owing  to  the  needs  of  the 
growing  organisms,  the  mononuclears  are  relatively  more 


THE   SCIENCE   AND  ART  OF  PROTEAL  THERAPY  155 

dant;  and  we  have  seen  that  such  is  the  condition  also  in  un- 
treated cases  of  cancer,  and  in  various  other  conditions  of  dis- 
turbed protein  metabolism,  including  intestinal  toxaemia;  subject, 
however,  to  the  modifying  consideration  that  an  excessive  stim- 
ulus may  for  a  prolonged  period  have  led  to  exhaustion  of  the 
blood-forming  organs,  bringing  about  a  leukopcenia. 

As  opposed  to  this  line  of  reasoning,  it  is  perhaps  worth  con- 
sidering that  the  polynuclear  appears  to  be  the  most  highly  dif- 
ferential of  leucocytes,  and  that  inferentially  it  might  be  sup- 
posed to  deal  with  the  higher  proteins  rather  than  with  fats  and 
hydrolysis  product.  Obviously,  the  question  calls  for  further 
experimental  evidence. 

As  to  the  different  types  of  large  monocytes,  I  am  disposed 
to  regard  lymphoidocytes,  myelocytes  of  the  different  types,  and 
cells  of  the  kind  designated  by  Papenheim  as  leucoblasts,  as  be- 
longing to  the  same  series  with  typical  large  monocytes,  the  latter 
being  mature  and  actively  functional  examples  of  this  type  of 
cell.  It  is  true  that  the  myelocyte  is  usually  regarded  as  of  the 
granular  series,  and  the  large  monocyte  as  of  the  non-granular ; 
but,  in  my  opinion,  this  distinction  does  not  connote  an  actual 
difference  of  origin  or  ultimate  structure,  but  only  divers  stages 
of  development. 

There  is  another  type  of  large  mononuclear  leucocytes  which 
I  believe  to  be  merely  an  overgrown  lymphocyte.  The  presence 
of  these  large  lymphocytes  indicates  activity  of  development  of 
the  lymphocyte  population.  Not  infrequently  in  the  course  of 
Proteal  treatment  it  will  be  observed  that  all  the  lymphocytes 
increase  in  average  size,  and  many  come  to  such  proportions 
as  to  be  classified  as  large  lymphocytes,  whereas  at  the  begin- 
ning there  was  but  a  minimum  number,  or  even  none  at  all,  of 
this  type  of  actively  functional  lymphocytes. 

Whereas  the  typical  large  monocyte  (including  the  so-called 
"transitional"  type),  with  its  relatively  deep-staining  nucleus  and 
basic  cytoplasm,  is  the  cell  that  I  like  to  see  represented  in  in- 
creasing coteries  under  Proteal  treatment,  I  am  disposed  to 
think  that  the  typical  large  lymphocyte  works  hand  in  hand,  so 
to  speak,  with  its  congener  in  dealing  with  the  foreign  proteins. 
Whether  one  type  of  cell  of  a  preference  deals  with  the  un- 
broken protein  molecule  and  another  with  the  partially  hydrolyzed 
molecule  (peptone,  proteose)  is  a  question  regarding  which  opin- 
ion must  as  yet  be  held  in  abeyance,  although  observations  are 
in  hand  that  at  least  prepare  the  way  for  the  ultimate  elucida- 
tion of  this  aspect  of  the  problem. 

The  fact  that  under  Proteal  treatment  there  is  coincident  in- 
crease in  numbers  and  betterment  of  quality  of  large  monocytes 
and  of  red  corpuscles,  suggests  a  possible  common  origin  for  these 


156      THE   PROTEOMORPHIC   THEORY   AND   THE   NEW    MEDICINE 

two  types  of  cells  in  similar  regions  of  the  bone  marrow.  Such 
origin  would  be  consistent  with  the  hypothesis  that  the  large 
monocytes  begin  and  the  red  corpuscles  complete  the  process  of 
protein  hydrolysis. 

That  under  normal  conditions  the  large  monocytes  are  few 
and  the  red  corpuscles  many,  may  be  provisionally  explained  on 
the  supposition  that  a  large  amount  of  protein  matter  normally 
enters  the  blood  stream  at  the  polypeptid  stage,  whereas  the 
amount  of  unbroken  protein  is  normally  very  small;  in  addition 
to  which  it  is  to  be  recalled,  of  course,  that  the  red  corpuscles 
have  the  further  function  of  carrying  oxygen. 

It  is,  of  course,  generally  accepted  that  the  polynuclears  orig- 
inate in  the  bone  marrow ;  but  the  fact  that  these  very  commonly 
decrease  in  number  while  the  large  monocytes  and  the  red  cor- 
puscles are  increasing  under  Proteal  treatment  suggests  an  in- 
dependent site  of  origin  as  a  possibility ;  with  the  alternative  pos- 
sibility that  the  genesis  of  different  types  of  leucocytes  may  be 
dependent  on  a  different  stimulus  to  the  mother  cell  rather  than 
upon  differences  in  the  mother  cells  themselves.  In  any  event, 
the  relative  decrease  of  polynuclears  (and  their  absolute  decrease 
when  they  originally  were  in  excess)  under  Proteal  treatment 
coincidentally  with  the  clinical  improvement  of,  let  us  say,  a 
cancer  case  in  which  the  neoplasm  is  regressing,  suggests  that 
whatever  share  the  polynuclear  may  have  in  the  decompounding 
of  the  foreign  protein  cell  may  be  accomplished  by  a  normal  com- 
plement or  even  a  subnormal  complement  of  these  particular 
agents.  The  reader  who  is  familiar  with  the  tables  published 
in  the  Monograph  will  recall  that  the  polynuclear  count  not  in- 
frequently falls  to  55  per  cent,  or  even  to  50  per  cent,  of  the 
total,  and  occasionally  drops  to  45  per  cent.,  and  even,  in  excep- 
tional instances,  to  39  per  cent. 

In  general,  as  has  been  noted,  under  Proteal  treatment,  the 
polynuclear  count  tends  toward  the  normal  or  slightly  subnormal 
status,  the  small  monocyte  population  being  subnormal,  and  the 
large  monocyte  showing  spectacular  increase.  For  example,  a 
table  published  in  the  Monograph,  showing  the  blood  count  in 
19  cases  of  cancer  after  an  average  treatment  of  186  days,  gave 
these  figures:  polynuclears,  57.1  per  cent.;  large  monocytes,  24.8 
per  cent. ;  small  monocytes,  15.7  per  cent. ;  eosinophiles  and  baso- 
philes  making  up  the  remaining  2.39  per  cent.  Another  table 
presenting  31  cases  after  an  average  of  152  days  of  protein 
treatment  showed :  polynuclears,  64.4  per  cent. ;  large  monocytes, 
18.3  per  cent.;  small  monocytes,  15.6  per  cent.  Still  another 
table,  showing  48  cases  of  various  kinds,  including  hyperthyroid- 
ism,  intestinal  toxaemia,  tuberculosis,  and  cancer  under  protein 
treatment  for  an  average  period  of  152  days  shows  the  following: 


THE   SCIENCE   AND  ART  OF   PROTEAL  THERAPY  157 

polynuclears,  63.4  per  cent. ;  large  monocytes,  16.9  per  cent. ;  small 
monocytes,  16.8  per  cent. 

In  each  of  these  groups  of  cases,  it  will  be  observed,  the 
striking  anomaly  is  the  preponderance  of  large  monocytes.  That 
fact,  however,  is  one  that  scarcely  needs  emphasizing  for  the 
reader  of  the  present  work.  That  such  an  increase  does  occur, 
as  the  direct  result  of  protein  treatment,  and  that  this  increase 
is  associated  in  a  beneficial  way  with  the  handling  of  foreign 
protein  products  in  the  system,  are  inferences  that  constitute 
the  substructure  of  this  book  and  the  guiding  principles  of  the 
investigations  on  which  it  is  based.  They  are  deductions  from  a 
wide  range  of  original  studies,  and  they  are  conceived  to  con- 
stitute a  significant  contribution  to  physiology,  pathology,  and 
therapeutics.  That  they  constitute  valid  observations  and  deduc- 
tions, I  entertain  not  the  remotest  doubt.  Nevertheless,  I  would 
repeat,  in  leaving  this  aspect  of  the  subject,  that  there  is  no 
necessary  association  between  the  validity  of  these  observations 
and  deductions  and  the  value  of  protein  medication  as  a  thera- 
peutic agency. 

In  my  original  studies,  clinical  observation  and  microscopical 
observation  have  gone  hand  in  hand.  Each  has  found  support 
in  the  other.  But  I  repeat  that  my  pioneer  work  with  the  micro- 
scope has  not  as  yet  been  checked  by  the  observation  of  any 
considerable  number  of  cases  in  the  hands  of  other  workers; 
whereas  the  clinical  results  have  been  duplicated  by  some  hun- 
dreds of  physicians  administering  Proteals  from  my  laboratory 
in  accordance  with  my  methods.  Under  such  circumstances,  it 
must  freely  be  admitted  that  the  clinical  findings  might  stand 
though  the  microscopical  findings  and  the  theoretical  explana- 
tions failed  of  corroboration.  As  I  have  stated,  no  one  should 
condemn  the  method  merely  because  he  does  not  agree  with  the 
theoretical  interpretation  here  presented. 

Having  made  that  concession,  however,  let  me  not  leave  the 
subject  without  reiterating  my  expectation  that  clinical  observa- 
tion and  microscopical  observation  will  both  find  abundant  war- 
rant in  the  findings  of  any  competent  observer  who  makes  scien- 
tific investigation  of  the  new  method ;  coupled  with  the  statement 
that  the  interpretation  of  the  observed  facts  in  the  light  of  the 
Proteomorphic  theory  constitutes  a  working  hypothesis  that  must 
hold  the  field  until  challenged  by  some  new  discovery  of  which 
we  have  no  present  inkling.  In  a  word,  repeating  the  phrase 
with  which  this  book  is  introduced,  and  modifying  it  to  fit  the 
present  purpose,  it  must  be  admitted  that  the  observations  and 
theories  of  protein  metabolism  and  Proteal  therapy  presented  in 
the  foregoing  pages  are  important  if  valid,  and  I  have  the  utmost 
confidence  that  they  are  valid. 


158      THE   PROTEOMORPHIC  THEORY   AND  THE    NEW    MEDICINE 

If  I  have  dwelt  rather  longer  on  this  aspect  of  the  subject 
than  might  have  been  expected  in  a  chapter  ostensibly  dealing 
with  practicalities,  it  is  because  I  would  reiterate  and  emphasize 
my  belief  that  protein  therapy  can  be  carried  out  to  best  advan- 
tage only  with  the  aid  of  the  microscope,  and  with  a  clear  under- 
standing of  the  underlying  principles  involved.  The  Proteals 
may  indeed  be  administered  empirically,  by  rule  of  thumb,  and 
with  only  clinical  results  as  a  guide;  but  they  may  be  admin- 
istered to  far  better  advantage  if  the  clinical  findings  are  checked 
day  by  day  or  week  by  week  with  microscopic  observations  of 
the  blood. 

RELATIVE  NON-TOXICITY  OF  THE  PROTEALS 

Let  us  turn  now  to  matters  that  to  the  average  reader  may 
seem  of  greater  interest  or  at  least  of  more  directly  practical 
character.  First  and  foremost,  there  is  the  matter  of  safety  of 
administration — implied  doubtless  in  the  foregoing  pages,  but 
not  hitherto  dealt  with  explicitly  and  in  detail. 

The  experiments  in  the  administration  of  proteins  to  dogs  and 
guinea  pigs  are  of  interest  in  this  connection.  It  has  been  re- 
ported by  independent  workers  that  very  small  doses  of  bac- 
terial toxins,  including  Coley's  fluid,  bring  about  a  condition  of 
toxicity,  with  notable  cachexia,  in  the  dog,  that  make  it  impos- 
sible to  continue  the  administration  for  a  considerable  length  of 
time  without  disastrous  consequences.  But,  on  the  other  hand, 
it  is  possible  to  administer  the  vegetable  protein  edestin  in  large 
doses  without  producing  unpleasant  symptoms  of  any  kind,  be- 
yond a  temporary  slight  chill  and  rise  in  temperature. 

I  have  administered  various  vegetable  proteins  (extracted  from 
more  than  a  score  of  plant  species  in  the  aggregate)  to  guinea 
pigs  week  after  week,  while  the  animals  maintained  perfect  health 
and  normal  growth ;  the  dosage  employed  relative  to  the  weight 
of  the  animals  being  from  fifty  to  one  hundred  times  the  max- 
imum Proteal  dose  employed  therapeutically. 

These  laboratory  observations  are  obviously  in  accord  with 
my  experience  and  that  of  many  scores  of  associated  physicians 
who  have  administered  proteals  to  patients  for  long  periods  of 
time ;  and  who  have  observed,  in  the  vast  majority  of  instances, 
a  marked  improvement  in  general  health,  and  the  disappearance 
rather  than  the  onset  of  cachexia.  Let  us,  however,  examine  this 
vital  aspect  of  the  subject  somewhat  more  at  length. 

In  the  original  presentation  of  the  Proteomorphic  theory,  as 
reproduced  in  the  present  book,  the  idea  was  elaborated  that  all 
foreign  proteins  are  primarily  toxic,  and  that  their  relative  tox- 
icity, in  their  effect  on  any  particular  organism,  is  determined 


THE   SCIENCE   AND  ART  OF   PROTEAL  THERAPY  159 

largely  by  the  duration  of  time  and  the  frequency  with  which 
that  organism  has  been  subjected  to  their  presence. 

This  principle  was  held  to  apply  to  the  proteins  that  serve 
for  food,  and  it  was  suggested  that  the  reason  why  vegetable 
proteins  in  the  foodstuffs  are  in  general  less  toxic  than  animal 
proteins  is  that  our  primitive  ancestors  doubtless  were  vege- 
tarians for  many  thousands  of  generations  before  they  became 
flesh  eaters.  Making  a  somewhat  more  elaborate  analysis,  it  is 
possible  to  make  the  application  to  many  familiar  foodstuffs.  We 
are  thus  provided,  for  example,  with  an  explanation  of  the 
familiar  clinical  fact  that  patients  suffering  from  intestinal  tox- 
aemia, with  its  attendant  sequels,  may  advantageously  be  placed 
on  a  vegetable  diet,  and  that  if  animal  proteins  are  allowed  milk 
and  cheese  are  more  wholesome  than  red  meat.  It  is  a  familiar 
practice  with  clinicians  to  permit  invalids  and  convalescents  to 
partake  of  these  animal  proteins,  followed  in  due  course  by  eggs, 
fish,  and  fowl,  before  permitting  the  use  of  beef  or  mutton ;  and 
it  would  appear  that  this  clinical  formula  finds  a  certain  measure 
of  support  in  an  analysis  of  the  probable  food  habits  of  our 
prehistoric  ancestors  in  successive  evolutionary  eras. 

This  point  of  view  is  recalled  in  the  present  connection  to 
emphasize  the  fact  that  I  have  not  overlooked  the  question  of 
the  toxicity  of  proteins  in  the  inauguration  and  elaboration  of 
the  principle  of  non-specific  protein  therapy.  From  the  outset, 
I  have  recognized  that  foreign  proteins  of  every  type  are  toxic 
and  must  be  handled  with  discretion.  But  I  have  found  them 
also  to  be  agents  having  unique  therapeutic  possibilities  when 
administered  in  proper  dosage.  And  it  is  hardly  necessary  to 
point  out  that  an  element  of  toxicity  is  no  barrier  to  the  use 
of  pharmaceutical  agents ;  else  we  must  forego  the  use  of  most 
of  the  best-accredited  drugs  in  our  equipment,  from  opium,  bella- 
donna, and  digitalis  to  diphtheria  antitoxin,  typhoid  vaccine,  and 
salvarsan. 

Nevertheless,  the  question  of  relative  toxicity  of  different  pro- 
teins is  a  highly  important  one.  My  experience  shows  that  there 
is  marked  difference  in  the  reaction  obtained  from  the  use  of 
vegetable  proteins,  none  of  which  could  be  considered  toxic  ex- 
cept in  the  general  sense  above  outlined.  Mustard  seed  proteins 
and  rape  seed  proteins,  for  example,  produce  a  much  less  severe 
reaction  (when  using  the  unbroken  molecule)  than  the  proteins 
of  alfalfa  seed  and  millet  seed.  It  does  not  follow,  however,  that 
the  former  are  the  more  valuable  agents  in  therapeutics.  Cases 
may  arise  in  which  it  is  desirable  to  produce  the  more  powerful 
stimulus  of  the  proteins  to  which  the  system  has  been  less  fa- 
miliarized by  past  usage.  In  point  of  fact,  in  the  case  in  ques- 
tion, the  alfalfa  and  millet  seed  proteins  have,  according  to  my 


160      THE    PROTEOMORPHIC   THEORY    AND   THE    NEW    MEDICINE 

observations,  far  greater  therapeutic  value  than  the  milder  pro- 
teins mentioned. 

It  should  be  explained  that,  whereas  the  introduction  of  vege- 
table proteins  therapeutically  into  the  parenteral  system  has  been 
practiced  extensively  for  a  period  of  only  about  three  and  a  half 
years,  many  cases  have  been  under  observation  in  which  treat- 
ment with  an  animal  protein  (sheep  serum)  dates  from  a  period 
much  more  remote — from  five  to  ten  years.  The  aggregate  ex- 
perience with  the  therapeutic  use  of  foreign  proteins  introduced 
parenterally  includes  upward  of  four  thousand  cases  directly 
observed  or  more  or  less  definitely  reported;  and  as  the  treat- 
ment of  individual  cases  has  usually  been  extended  over  terms 
of  weeks  or  months,  a  single  patient  sometimes  receiving  up- 
ward of  300  doses,  it  will  be  seen  that  practical  experience  is 
sufficiently  extensive  to  justify  deductions  meriting  confidence. 

The  general  conclusion  which  I  wish  to  state  in  unequivocal 
and  emphatic  terms  is  that  patients  subjected  for  prolonged 
periods  to  the  hypodermic  administration  of  foreign  proteins, 
including  sheep  serum  and  a  variety  of  vegetable  proteins,  show 
no  evidence,  either  clinical  or  hematological,  of  toxicity  in  the 
ordinary  sense  of  the  word,  but,  on  the  contrary,  are  robust 
of  physique  and  normal  of  blood.  Meantime  the  pathological 
symptoms  for  which  the  proteins  were  administered  may  have 
disappeared  altogether  or  have  been  markedly  modified  for  the 
better. 

This,  after  all,  is  what  might  have  been  predicated  from  a 
knowledge  of  the  fact  that  a  certain  amount  of  unbroken  pro- 
protein  from  the  food  finds  its  way  regularly  into  the  parenteral 
system  from  the  digestive  tract.  In  other  words,  every  indi- 
vidual, in  health  and  in  disease,  is  more  or  less  subject  to  con- 
tinuous cytogenic  stimulus  from  the  presence  of  the  food  proteins 
in  his  parenteral  system.  To  be  sure,  it  has  been  suggested  (by 
Metchnikoff  originally)  that  this  fact  has  to  do  with  the  ulti- 
mate development  of  symptoms  of  senescence  with  the  passing 
of  the  years;  and  it  is  my  personal  belief  that  the  presence 
of  foreign  proteins  in  excess,  taken  as  food  products  with  the 
ordinary  diet,  is  responsible  for  a  large  measure  of  the  malad- 
justments that  are  incident  to  and  coincident  with  the  devel- 
opment of  what  we  term  old  age.  Be  that  as  it  may,  however, 
the  case  records  cited  in  this  book  (together  with  those  epit- 
omized in  tables  of  the  Monograph)  would  appear  to  give  final 
answer  to  the  question  whether  a  prolonged  use  of  proteanti- 
gens  in  therapeutic  dosage  constitutes  a  measure  necessarily  det- 
rimental to  the  patient.  The  records  seem  to  show  that,  quite 
on  the  contrary,  such  administration  may  be  in  the  highest  de- 


THE   SCIENCE   AND  ART  OF   PROTEAL  THERAPY  161 

gree  beneficial,  and  that  the  judicious  use  of  proteantigens  may 
stimulate  the  blood-forming  mechanism  to  the  effective  combating 
of  toxins  both  of  bacterial  and  non-bacterial  origin  against  which 
no  other  measure  of  corresponding  efficacy  is  available. 

I  have  already  presented  tables  showing  that  the  modifications 
of  the  blood  count  under  proteantigen  treatment  may  be,  and 
frequently  are,  progressive  in  what  I  consider  the  right  direction. 
I  am  preparing  for  publication  in  the  new  edition  of  the  Mon- 
ograph more  elaborate  series  of  tables  in  which  blood  counts  of 
various  patients  are  arranged  sequentially  as  to  time;  beginning 
with  a  series  of  counts  of  untreated  cases,  and  going  on  day  by 
day  to  cases  that  have  been  under  treatment  for  a  term  of 
months.  For  convenience  of  observation,  these  cases  are  ar- 
ranged in  successive  groups  by  ten-day  periods.  This,  it  will 
be  understood,  is  a  purely  arbitrary  division,  made  merely  to 
give  opportunity  to  classify  results  and  show  at  a  glance  the 
general  -effect  of  treatment  given  a  variety  of  cases  for  shorter 
and  longer  periods  of  time.  It  will  be  seen  that,  generally  speak- 
ing, there  is  a  progressive  or  cumulative  effect  observable ;  that, 
in  other  words,  cases  that  have  been  the  longest  under  treat- 
ment are,  on  the  average,  those  that  show  the  most  pronounced 
modification  of  the  blood  count  in  the  direction  of  (a)  higher 
haemoglobin  index,  (b)  increase  of  red  corpuscles,  (c)  modifica- 
tion toward  the  normal  of  the  leucocyte  count,  with  (d)  relative 
increase  of  mononuclear  leucocytes,  and  in  particular  marked 
increase  of  large  mononuclears. 

If  these  facts  are  interpreted  in  the  light  of  the  Proteomorphic 
theory,  it  appears  that  the  conglomerate  group  of  patients  here 
under  consideration  have  benefited  progressively  by  the  prote- 
antigen treatment,  and  that  those  that  have  been  treated  more 
or  less  regularly  for  periods  of  six  months,  a  year,  and  even 
two  years,  are  in  better  condition,  as  regards  their  blood  count, 
than  those  treated  for  a  shorter  period.  When  it  is  further  stated 
that  these  patients,  observed  as  to  their  clinical  condition,  show 
a  similar  status  of  improvement,  the  case  for  the  non-toxicity  of 
proteantigens  of  types  herein  referred  to  (chiefly  egg  albumen, 
milk  albumen,  sheep  serum,  and  the  Proteals)  may  be  considered 
to  be  fairly  established. 

I  may  add,  by  way  of  auxiliary  evidence,  that  of  the  hun- 
dreds of  physicians  who  have  used  the  Proteals  from  my  labora- 
tory no  one  has  ever  reported  a  reaction  giving  occasion  for  the 
slightest  alarm,  much  less  a  lethal  effect;  whereas  testimony  to 
the  beneficial  effects  resulting,  seemingly  in  direct  consequence 
of  the  administration  of  the  Proteals,  has  been  so  nearly  unani- 
mous as  to  satisfy  the  most  optimistic  anticipations. 


162    THE  PROTEOMORPHIC  THEORY  AND  THE  NEW  MEDICINE 

THE  PREPARATION  OF  THE  PROTEALS 

It  is  perhaps  unnecessary  here  to  go  into  details  concerning 
the  various  methods  of  extracting  vegetable  proteins  that  have 
been  employed  at  one  time  and  another  in  my  laboratory.  The 
chief  facts  of  importance  attach  to  the  method  that  has  super- 
seded others,  and  has  been  employed  in  preparing  the  Proteals 
supplied  to  the  profession  during  the  past  year,  the  results  of 
the  use  of  which  are  summarized  in  succeeding  pages. 

The  method  consists  in  the  extraction  of  the  proteins  by  boil- 
ing the  ground  seeds  or  other  plant  products  in  a  very  dilute 
solution  of  hydrochloric  acid.  Best  results  have  been  attained 
with  most  seeds  by  using  50  grams  of  the  powder  to  the  liter 
of  water,  and  adding  from  40  to  80  cubic  centimeters  of  ten 
per  cent,  hydrochloric  acid.  With  plant  products  other  than 
seeds,  such  as  alfalfa  meal,  20  cubic  centimeters  of  the  dilute 
acid  suffice.  The  mixture  is  boiled  in  a  glass  flask  for  four 
hours. 

The  decoction  contains,  of  course,  a  mass  of  vegetable  detritus 
that  must  be  removed  by  filtering.  There  is  marked  variation 
in  different  products  in  their  facility  of  filtering.  With  some 
it  is  necessary  to  refilter  two  or  three  times.  The  final  filtrate  is 
neutralized  with  10  per  cent,  solution  of  sodium  hydroxide.  Just 
beyond  the  neutralization  point  a  precipitate  forms,  part  of  which 
is  redissolved.  The  solution,  meantime,  becomes  of  a  darker 
color,  varying  from  amber  to  a  deep  claret  according  to  the 
constituents. 

Either  before  or  after  filtering,  as  a  matter  of  convenience, 
the  solution  is  evaporated  at  low  temperature  under  a  hot  air 
draft  until  it  bulks  about  300  cubic  centimeters  (varying  from 
200  to  400  with  different  products).  The  solution  has  usually 
become  slightly  acid  again,  and  it  is  necessary  once  more  to 
neutralize  with  sodium  hydroxide.  It  is  important  that  slight 
alkalinity  should  be  attained  and  preserved ;  otherwise,  the  extract 
will  be  painful  on  hypodermic  administration. 

The  Kjeldahl  nitrogen  test  is  now  made,  after  which  the  solu- 
tion is  either  further  evaporated  or  diluted  with  normal  salt 
solution,  as  the  case  may  require,  to  bring  it  to  the  standard 
strength  of  three  milligrams  of  nitrogen  to  the  cubic  centimeter ; 
indicating  a  protein  content  of  slightly  less  than  two  per  cent. 

The  extract  thus  standardized  is  placed  in  ampules  and  sealed 
in  a  Bunsen  flame ;  then  sterilized  discontinuously  for  three  days 
in  an  ordinary  sterilizer. 

There  are,  as  a  matter  of  course,  tricks  of  manipulation  facil- 
itating the  preparation  of  the  Proteals  that  vary  somewhat  with 
the  different  products ;  but,  as  will  be  seen,  the  process  is,  on 


THE    SCIENCE   AND  ART  OF   PROTEAL  THERAPY  163 

the  whole,  a  very  simple  one.  It  may  readily  be  duplicated  in 
any  laboratory  having  a  moderate  equipment  for  physiological 
chemistry. 

The  proteins  thus  prepared  contain  alkali  albumens,  proteoses, 
and  a  variable  quantity  of  peptones.  It  is  obvious  that  the  rela- 
tive percentages  of  the  products  of  partial  hydrolysis  will  vary 
with  the  degree  of  concentration  of  acids  in  the  original  medium 
and  the  length  of  time  of  boiling.  The  whole-plant  products, 
like  alfalfa  meal,  being  boiled  in  weaker  acid  solution,  are  less 
extensively  hydrolyzed,  and  their  proteins  have  been  observed 
to  be  much  more  likely  to  produce  a  local  anaphylactic  response. 
Whether  there  are  compensatory  advantages  in  this  is  a  ques- 
tion that  I  am  not  as  yet  prepared  to  answer  definitely;  but  I 
have  observed  a  good  many  cases  in  which  the  local  reaction 
appeared  to  be  followed  by  a  beneficial  systemic  response. 

In  this  connection  it  may  be  observed  that  the  earlier  ex- 
tracts, prepared  without  boiling,  in  simple  salt  solution  or  in 
solutions  of  sodium  hydroxide,  and  containing  the  full-sized  pro- 
tein molecule,  produced  a  much  more  severe  local  reaction,  and 
occasionally  a  general  anaphylactic  reaction;  and  that  it  was  at 
first  supposed  that  the  production  of  a  pronounced  reaction  was 
therapeutically  desirable.  The  independent  workers  who  in  June, 
1916,  and  subsequently  reported  the  use  of  proteoses  and  of 
bacterial  vaccines  as  non-specific  agents,  as  in  the  treatment  of 
typhoid  fever  and  arthritis,  have  employed  a  dosage  (one  or  two 
c.c.  of  a  four  per  cent,  albumen  solution)  that  produced  very 
marked  systemic  effects,  as  well  as  a  pronounced  leucocytosis ; 
and  some  of  them  at  least  have  associated  the  observed  clinical 
benefits  with  the  febrile  reaction. 

I  have  no  doubt  that  there  are  cases  where  heroic  dosage  is 
desirable,  but  in  general  the  application  of  Proteal  therapy,  as 
I  use  it,  calls  for  small  doses,  not  producing  marked  systemic 
reactions. 

The  Proteal  that  has  been  used  most  extensively  during  the 
past  year  and  a  half,  and  sent  out  from  my  laboratory  in  largest 
quantities  to  members  of  the  profession,  is  No.  45,  the  combina- 
tion of  equal  parts  of  the  proteins  of  alfalfa  seed,  alfalfa  meal, 
and  millet  seed.  The  same  combination  with  the  addition  of  the 
proteins  of  rape  seed  and  mustard  seed  bears  the  laboratory  num- 
ber 65.  A  newer  combination,  much  less  extensively  tested  as  yet, 
contains  the  proteins  of  red  clover  seed,  cotton  seed,  flax  seed, 
hemp  seed,  and  carrot  seed,  and  bears  the  number  75.  A  still 
more  comprehensive  combination,  containing  equal  parts  of  the 
proteins  of  the  ten  different  types  just  listed  (a  mixture,  in 
other  words,  of  No.  65  and  No.  75),  is  known  as  Proteal  No.  100. 

The  question  naturally  arises  as  to  whether  there  are  thera- 


164      THE   PROTEOMORPHIC  THEORY   AND  THE    NEW    MEDICINE 

peutic  advantages  in  using  a  combination  of  proteins  rather  than 
a  single  protein.  I  believe  that  experience  does  not  as  yet 
justify  a  positive  answer.  I  have  studied  the  matter  very  care- 
fully through  observation  both  of  clinical  symptoms  and  the 
blood  response,  and  I  am  not  prepared  to  say  positively  that  I 
have  seen  decisive  evidence  of  a  difference,  qualitative  or  quan- 
titative, between,  for  example,  the  use  of  Proteal  No.  39,  which 
contains  only  the  protein  of  alfalfa  seed,  and  Proteal  No.  45, 
which  contains  also  the  proteins  of  alfalfa  meal  and  millet  seed. 
It  is  difficult  to  avoid  the  feeling  that  there  must  be  a  differ- 
ence, but  this  may  be  based  merely  on  a  preconception.  I  have 
thought  it  worth  while  to  test  the  validity  of  the  preconception 
by  making  the  elaborate  combinations  above  listed,  and  numer- 
ous others.  I  think  the  matter  will  not  be  definitely  settled  until 
many  thousands  of  cases  have  been  treated  with  single  proteins 
and  with  proteins  in  combination.  There  would  seem  to  be 
theoretical  warrant  for  the  assumption  that,  inasmuch  as  each 
protein  has  its  own  individual  response,  a  combination  of  pro- 
teins would  produce  a  more  varied  and,  in  the  aggregate,  a  more 
pronounced  response  than  a  single  protein.  But  whether  or  not 
this  should  prove  to  be  the  fact,  there  is  nevertheless  abundant 
reason  for  making  the  combinations,  inasmuch  as  they  give  oppor- 
tunity for  the  introduction  of  a  new  type  of  protein  from  time 
to  time,  in  accordance  with  the  established  therapeutic  principle 
that  it  is  desirable  to  change  the  type  of  protein,  or  introduce 
a  new  type,  when  a  certain  degree  of  immunization  or  cytogenic 
apathy  has  been  produced. 

A  convenient  practical  method,  for  example,  is  to  begin  treat- 
ment of  a  case,  let  us  say,  of  tuberculosis,  with  Proteal  No.  39, 
alfalfa  seed  protein;  shifting  presently  to  a  combination  of 
alfalfa  seed  and  alfalfa  meal  (Proteal  No.  60),  and  then  in  due 
course  to  No.  45,  which  introduces  millet  seed  protein  as  an 
additional  element.  A  little  later  the  shift  may  be  made  to 
Proteal  No.  65,  which,  still  retaining  the  alfalfa  and  millet  pro- 
teins, introduces  also  the  proteins  of  rape  seed  and  mustard 
seed.  Still  later  an  entire  shift  may  be  made  to  No.  75,  with  its 
five  new  proteins,  or  to  No.  100,  which  retains  the  original  pro- 
teins in  relatively  reduced  quantities  and  introduces  five  new  ones. 

An  alternative  procedure,  which  has  been  observed  to  work 
well  in  many  cases,  is  to  begin  with  a  combination,  say  No.  45 
or  No.  65,  and  after  a  time  to  shift  to  a  single  one  of  the  con- 
stituents. For  example,  begin  with  the  combination  containing 
alfalfa  seed,  alfalfa  meal,  millet  seed,  rape  seed,  and  mustard 
seed  (No.  65),  and  presently  shift  to  No.  39,  alfalfa  seed  protein 
alone,  beginning  with  a  relatively  small  dose  and  increasing  grad- 
ually, until,  obviously,  at  maximum  dosage  the  maximum  re- 


THE   SCIENCE   AND  ART   OF   PROTEAL  THERAPY  165 

sponse  from  that  particular  protein  may  be  expected.  After 
that  one  may  shift  to  millet  seed  protein  (No.  38)  or  rape  seed 
protein  (No.  42),  and  so  on.  The  advantages  of  such  a  transi- 
tion are  that  it  enables  one  to  begin  with  a  mild  general  response 
and  presently  to  get  the  maximum  effect  from  an  individual 
protein. 

The  response  to  the  combined  proteins  would  be,  theoretically, 
varied  and  comprehensive ;  the  response  to  the  single  protein 
restricted,  but  relatively  intense. 

The  experienced  physician  will  use  his  own  ingenuity  in  mak- 
ing application  of  these  principles,  just  as  he  does  in  combining 
drugs  in  his  ordinary  prescriptions.  Every  skilful  practitioner 
uses  combinations  of  drugs  having  allied  effects,  in  the  confident 
belief  that  he  is  attaining  certain  results  at  least  a  little  better 
than  could  be  secured  from  any  one  of  the  individual  constit- 
uents. Yet  he  might  find  it  difficult  to  prove  this.  Similarly, 
some  users  of  the  Pro  teals  come  to  feel  that  they  get  results 
from  combinations  that  they  do  not  get  from  the  individual 
proteins.  I  repeat  that  it  remains  for  the  future,  with  its  analysis 
of  thousands  of  cases,  to  justify  or  refute  this  belief. 

Meantime  it  is  not  in  the  least  in  doubt  that  each  type  of 
protein  produces  its  own  individual  response,  and  that  one  pro- 
tein may  not  be  substituted  for  another  indifferently.  That  a 
system  immunized  to  large  doses  of  proteins  of  one  kind  or 
combination,  for  example,  will  show  the  most  vigorous  reaction 
when  a  new  protein  is  introduced,  has  been  demonstrated  over 
and  over  in  my  experience,  particularly  in  the  early  days  when 
working  with  the  unbroken  proteins. 

This  is  tantamount  to  saying  that,  whereas  the  Proteals  are 
thus  standardized  on  the  basis  of  the  same  amount  of  protein 
in  each,  it  does  not  follow  that  each  one  is  the  equivalent  of  the 
other  in  its  therapeutic  action.  It  is  my  opinion,  as  the  reader  of 
the  foregoing  pages  is  aware,  that  the  protein  response  is  always 
similar  in  character  and  to  be  interpreted  in  the  same  physiolog- 
ical terms.  But  it  has  already  been  pointed  out  again  and  again 
that  some  Proteals  produce  much  more  active  response  than 
others.  The  explanation  offered  has  been  that  proteins  to  which 
the  system  has  longest  been  accustomed  and  most  continuously 
experienced  will  produce  the  least  striking  reaction. 

SPECIFIC  PROPERTIES  OF  NON-SPECIFIC  PROTEINS 

To  speak  of  the  specific  properties  of  non-specific  proteins 
would  appear  to  be,  on  its  face,  a  contradiction  of  terms.  But 
the  phrase  has  definite  meanings  that  are  clearly  intelligible.  The 
word  "specific"  as  employed  in  connection  with  the  use  of  pro- 


166      THE   PROTEOMORPHIC  THEORY   AND  THE   NEW   MEDICINE 

tein  remedies  refers,  as  is  well  known,  to  the  use  of  the  bodies 
or  toxins  of  definite  character  of  pathogenic  bacteria  to  combat 
conditions  associated  with  the  activities  of  the  same  type  of 
bacteria.  The  use  of  anti-typhoid  vaccine  either  as  a  preventive 
against  typhoid  fever  or  as  a  curative  agent  when  typhoid  fever 
has  actually  developed,  is  the  classical  illustration  of  the  specific 
use  of  a  specific  protein  remedy. 

But  the  same  vaccine  may  be  used,  and  in  point  of  fact  has 
been  used  with  apparent  effectiveness  in  the  treatment  of  rheuma- 
toid conditions;  and  in  such  a  case  the  vaccine  is  used  non- 
specifically.  In  the  latter  case  the  response  evoked  or  desired 
has  no  association  with  the  typhoid  bacillus,  but  is  a  general 
protein  response.  Doubtless  there  is  a  specific  response  also,  but 
this  is  purely  incidental  and  does  not  enter  into  the  calculations 
of  the  therapeutist. 

When  vegetable  proteins  extracted  from  the  seeds  or  sub- 
stances of  higher  plants  are  used  there  is  obviously  no  chance 
for  a  specific  response  in  the  sense  in  which  the  word  has  just 
been  defined.  Observation  shows  that  there  are  certain  very 
characteristic  modifications  of  the  blood  that  occur  in  response 
to  the  parenteral  introduction  of  any  of  these  foreign  proteins, 
and  that  similar  modifications  are  brought  about  by  the  intro- 
duction of  various  animal  proteins,  for  example,  sheep  serum.  In 
the  practical  use  of  the  Proteals  it  has  been  found  possible  to 
substitute  one  for  another,  the  selection  of  the  particular  type 
of  protein  to  be  used  in  beginning  treatment  of  a  given  case 
being  to  a  considerable  extent  a  matter  of  indifference.  I  early 
observed,  however,  that  some  types  of  vegetable  proteins  pro- 
duced a  very  much  more  pronounced  anaphylactic  response  than 
others,  and  I  soon  found  myself  selecting  one  protein  or  another 
with  definite  reference  to  the  observed  condition  or  suspected 
idiosyncrasies  of  the  particular  patient. 

This  obviously  implies  a  recognition  of  specific  differences 
among  the  vegetable  proteins  used  non-specifically. 

Further  proof  of  such  differences  were  found  in  the  fact  that 
an  individual  patient  sometimes  responded  much  more  actively  to 
one  type  of  protein  than  another.  An  injection  of  alfalfa  pro- 
teins, for  example,  might  cause  a  marked  local  reaction,  whereas 
when  mustard  seed  or  rape  seed  protein  was  substituted  no  reac- 
tion occurred.  Further  proof  of  the  specific  action — in  the  usual 
sense  of  the  word — was  given  when  it  was  found  that  the  patient 
who  had  become  in  a  measure  immunized  to  the  effect  of  one 
protein  showed  new  response  on  exhibition  of  another  protein. 

Reasoning  from  analogy,  we  may  suppose  that  the  relative 
non-toxicity  of  proteins  from  food  plants  will  be  shared  in  some 
measure  by  proteins  from  botanically  related  species  of  plants. 


THE    SCIENCE   AND   ART   OF   PROTEAL   THERAPY  167 

Thus  food  plants  and  their  allies  would  furnish  proteins  to  which 
the  system  was  relatively  immune;  whereas  the  plants  lying  bo- 
tanically  rather  far  afield  from  the  food  plants  would  furnish 
proteins  of  relative  activity  or  toxicity.  Experience,  so  far  as 
it  has  gone,  tends  to  confirm  this  supposition.  In  selecting  plants 
for  the  development  of  new  Proteals,  I  am  guided  by  this  prin- 
ciple. Among  the  newer  extracts,  for  example,  the  clover  pro- 
teins may  fairly  be  expected  to  produce  more  pronounced  re- 
sponse than  the  proteins  of  oats  and  wheat. 

It  may  be  added  that  the  theory  finds  further  confirmation  in 
the  fact  that  the  proteins  of  white  of  egg  and  of  milk,  which 
I  have  used  somewhat  extensively  in  alternation  with  the  vari- 
ous Proteals,  give  a  still  milder  reaction,  so  I  was  accustomed, 
while  experimenting  with  them,  to  standardize  them  in  a  three 
per  cent,  solution  and  give  them  in  the  same  dosage  that  was 
employed  with  the  two  per  cent.  Proteals. 

All  this  clearly  implies  specific  differences  in  the  therapeutic 
action  of  the  non-specific  proteins.  If  the  conclusions  just  given 
are  justified,  it  is  obvious  that  here  is  a  field  for  investigation 
of  very  wide  possibilities.  The  plants  from  which  I  have  hith- 
erto extracted  proteins  for  therapeutic  use  number  fewer  than 
thirty  species ;  it  would  be  difficult  to  put  a  limit  upon  the  num- 
ber that  might  advantageously  be  tested. 

THE  ADMINISTRATION  OF  THE  PROTEALS 

It  is  my  custom  to  begin  the  treatment  of  every  new  case  with 
doses  of  only  three  or  four  minims  of  any  one  of  the  proteals; 
and  administering  treatment  usually  on  alternate  days,  but  some- 
times daily,  to  increase  minim  by  minim,  or,  if  there  is  no  reac- 
tion, two  or  three  minims  at  a  time  till  a  maximum  dose  is 
attained. 

The  size  of  the  maximum  dose  varies  with  the  individual  case. 
Where  there  is  profound  protein  toxaemia,  as  in  a  well-developed 
cancer  subject,  it  is  usually  desirable  to  run  the  dose  up  rather 
rapidly  to  10,  15,  or  even  20  minims ;  sometimes  a  good  deal 
beyond  this.  Doses  of  60  and  even  90  minims  of  the  original 
proteal  extract  have  been  given.  I  formerly  thought  it  desirable 
to  push  the  dosage  until  a  fairly  severe  general  reaction  (rise  of 
temperature,  quick  pulse,  chill)  was  produced  on  at  least  one  occa- 
sion. Prolonged  experience,  however,  in  which  clinical  symp- 
toms were  observed  in  connection  with  the  blood-count  modifica- 
tions, leads  me  to  question  whether  this  is  usually  desirable, 
even  in  cases  of  malignancy;  and  it  is  not  in  the  least  degree 
necessary  to  secure  a  general  reaction  in  dealing  with  the  milder 


168      THE    PROTEOMORPHIC   THEORY   AND   THE    NEW    MEDICINE 

types  of  toxaemias  associated  with  secondary  anaemias  and  neuras- 
thenia. 

In  cases  of  the  latter  type  a  maximum  dose  of  5  to  8  minims 
usually  suffices,  and  often  results  of  the  most  conspicuous  and 
well-defined  character  may  be  attained  with  a  dosage  of  only  4 
or  5  minims. 

In  general,  my  present  tendency  is  to  use  small  doses,  and  if 
necessary  give  them  more  frequently,  rather  than  to  force  the 
dosage  to  heroic  proportions.  With  the  new  proteals  there  is  no 
objection  to  frequent  administration,  as  the  giving  of  the  hypo- 
dermic is  practically  painless. 

Probably  the  most  satisfactory  method  of  treatment,  whether 
of  simple  toxaemias  or  malignant  ones,  is  to  administer  a  given 
Proteal  in  gradually  increasing  doses  until  the  maximum  dose 
considered  desirable  in  a  given  case  is  reached — that  is  to  say,  a 
dose  that  produces  a  satisfactory  clinical  progress  and  character- 
istic modifications  of  the  blood  count;  to  hold  to  this  maximum 
dose  for  a  week  or  ten  days ;  and  then  to  shift  to  another  pro- 
teal,  beginning  with  a  dose  of  three  or  four  minims  and  working 
up  the  scale  as  before.  It  should  be  remembered  that  each  pro- 
tein elicits  its  own  response,  and  that  a  patient  relatively  im- 
munized to,  let  us  say,  mustard  seed  or  rape  seed  proteins  may 
react  vigorously  to  the  protein  of  alfalfa.  The  rule  is,  in  begin- 
ning with  a  new  protein,  to  start  with  a  minimum  dose,  no  mat- 
ter how  thoroughly  accustomed  the  patient  is  to  the  administra- 
tion of  other  proteins. 

Similarly  if  the  patient  has  discontinued  the  Proteal  treatment 
for  a  considerable  period,  and  then  begins  it  again,  even  with 
the  same  Proteal,  it  is  well  to  start  in  with  a  small  dose,  but 
in  this  case  the  dosage  may  be  increased  much  more  rapidly 
than  with  a  new  patient. 

It  is  my  routine  practice  to  administer  the  Proteals  by  fairly 
deep  subcutaneous  hypodermic  injection  into  the  back  of  the 
upper  arm.  Intravenous  injection  has  sometimes  been  employed, 
but  this  produces  a  severe  anaphylactic  reaction  the  desirability 
of  which  is  doubtful  unless  in  very  obstinate  and  intractable 
cases.  I  do  not  advocate  or  practice  the  method  of  heroic  dosage, 
with  emphatic  anaphylactic  reaction,  that  a  few  physicians  who 
in  recent  months  have  advocated  non-specific  protein  therapy  with 
the  use  of  vaccines  appear  to  have  employed.  My  own  experi- 
ence, based  on  study  of  a  far  larger  number  of  cases  than  have 
elsewhere  been  treated  with  non-specific  proteins  in  the  entire 
world,  leads  me  to  conclude  that  the  milder  method  of  admin- 
istration is  equally  efficacious  in  the  end,  while  being  devoid  of 
unpleasant  features. 

It  is  obvious  that  patients  suffering  from  a  simple  anaemia 


THE   SCIENCE   AND  ART  OF   PROTEAL  THERAPY  169 

or  a  mild  intestinal  toxaemia  would  not  submit  to  a  treatment 
that  involved  the  production  of  a  severe  anaphylactic  reaction. 
In  such  a  case  the  remedy  would  be  considered  worse  than  the 
disease.  Fortunately  nothing  of  the  kind  is  either  necessary  or 
desirable.  Such  a  patient  undergoing  Proteal  treatment  submits 
to  nothing  more  disagreeable  than  a  painless  hypodermic,  fol- 
lowed at  worst  by  a  very  slight  tenderness  at  the  point  of  injec- 
tion, and  with  no  general  reaction  whatever  except  the  pleasurable 
one  of  increased  bouyancy  and  enhanced  sense  of  well  being. 

Such,  then,  are  the  essentials  of  the  technique  of  Proteal  ther- 
apy at  present  developed.  I  greatly  mistake  if  the  method  does 
not  constitute  a  marked  advance  upon  any  therapeutic  measure 
hitherto  available  for  treatment  of  the  varied  groups  of  con- 
ditions of  disturbed  protein  metabolism — ranging  from  simple 
anaemias  to  tuberculosis  and  cancer — to  which  it  is  applicable. 

Let  us  now  turn  from  generalities  to  particulars  and  consider 
very  briefly  the  salient  aspects  of  the  application  of  the  Proteal 
method  to  the  different  types  of  protein  toxaemia  in  question. 

PROTEAL  TREATMENT  OF  CANCER 

The  reader  is  aware  that  the  fundamental  fact  upon  which 
Proteal  therapy  is  based  is  that  the  parenteral  administration 
of  a  foreign  protein  in  suitable  doses  leads  to  a  systemic  response 
characterized  by  rejuvenation  of  the  blood  corpuscles.  The  indi- 
rect result  of  such  rejuvenation  is,  in  effect,  the  enhancement 
of  the  phagocytic  and  enzymic  forces  with  which  the  body  com- 
bats protein  invasion  of  all  kind.  This  includes,  obviously,  cells 
of  the  type  called  malignant. 

Incidentally,  therefore,  Proteal  therapy  is  applicable  in  the 
treatment  of  cancer.  As  I  have  written  another  book  on  this 
aspect  of  the  subject,  I  shall  here  summarize  my  experience  in 
this  field  very  briefly.  In  so  doing,  perhaps,  I  may  be  permitted 
to  incorporate  matter  from  a  popular  article  in  which  I  gave  a 
condensed  account  of  my  experience.  Possibly  the  present 
reader,  sated  with  technicalities  of  recent  pages,  will  find  this 
popular  summary  a  refreshing  change.  The  reader  who  wishes 
fuller  and  more  technical  information  as  to  the  status  of  the 
Proteal  treatment  of  cancer  may  turn  to  the  Monograph  just  re- 
ferred to,  which  under  the  original  title  of  The  Proteal  Treatment 
of  Cancer  and  Allied  Conditions,  is  about  to  be  issued  in  a  sec- 
ond edition. 

The  condensed  popular  presentation  which,  taken  in  connec- 
tion with  repeated  references  in  other  chapters,  seems  fairly 
adequate  for  the  present  purpose,  is  the  following: 

Wherever  the  cancerous  condition  develops  there  is  always  pro- 


170      THE   PROTEOMORPHIC  THEORY  AND  THE   NEW   MEDICINE 

found  disturbance  of  the  blood,  evidenced  among  other  things 
by  modifications  in  the  quality  of  the  red  corpuscles  and  the  rela- 
tive numbers  of  the  different  types  of  white  corpuscles.  Cancer 
is  never  a  merely  local  condition. 

To  put  the  matter  in  untechnical  language,  the  corpuscles  fight 
the  developing  cancer  cells;  if  they  win,  the  cancer  is  eliminated. 
The  development  of  a  cancer  of  tangible  size  is  proof  positive 
that  the  corpuscles  have  lost  the  fight.  It  may  plausibly  be 
argued  that  if  a  way  could  be  found  to  increase  the  cohorts  of 
corpuscles,  and  to  increase  their  fighting  capacity,  the  tide  of 
battle  might  be  turned,  and  the  corpuscles,  hitherto  defeated, 
might  now  become  victorious  against  the  cancer  cells. 

When  the  Proteals  are  administered  hypodermically,  rejuve- 
nation of  the  cohorts  of  blood  corpuscles  takes  place.  That  is  a 
simple  matter  of  fact,  which  I  have  demonstrated  hundreds  of 
times  under  the  microscope.  My  observations  have  been  con- 
firmed by  numerous  independent  workers.  It  has  further  been 
observed  that  the  physical  condition  of  the  cancer  patient  very 
generally  undergoes  a  marked  change  soon  after  the  Proteal 
treatment  is  instituted.  Even  where  cancer  had  reached  a  late 
stage,  perhaps  following  successive  operations,  and  was  now 
inoperable  and  supposedly  hopeless,  marked  changes  of  favor- 
able character  have  been  observed  repeatedly. 

I  have  personally  collected  and  published  reports  of  766  such 
cases,  treated  by  more  than  one  hundred  and  fifty  physicians, 
showing  that,  in  the  estimate  of  the  physicians  themselves,  64 
per  cent,  of  these  "hopeless"  cases  showed  conspicuous  improve- 
ment under  the  non-specific  protein  treatment. 

In  a  certain  number  of  these  cases  the  improvement  continued 
until  the  physician  regarded  the  patient  as  clinically  well.  The 
percentage  of  such  seeming  recoveries  was  small;  but  that  a 
single  supposedly  "hopeless"  case  could  be  thus  reported  in 
the  early  stages  of  the  use  of  a  new  method  of  treatment  was 
in  the  highest  degree  enheartening.  To  the  observers  of  such  a 
transformation  the  result  seems  to  border  on  the  miraculous. 

Even  where  the  ultimate  results  fell  short  of  this  there  were 
temporary  effects  in  a  large  proportion  of  cases  that  seemed 
decidedly  worth  while.  For  example,  in  response  to  a  special 
request,  I  received  reports  at  one  time  from  142  physicians  cov- 
ering 284  inoperable  cases.  The  reports  came  from  37  States 
and  from  several  provinces  of  Canada,  all  the  physicians  being 
men  of  recognized  standing.  The  specific  preliminary  results  in 
this  group  of  cases  were  as  follows: 

Where  pain  was  present,  it  was  favorably  modified  by  the 
non-specific  protein  treatment  in  77.4  per  cent,  of  all  cases.  Gen- 
erally the  use  of  stupefying  opiates  could  be  discontinued.  Where 


THE   SCIENCE  AND  ART  OF  PROTEAL  THERAPY  171 

an  offensive  discharge  was  present,  it  was  favorably  modified 
in  85.6  per  cent,  of  cases.  The  general  health  of  the  patient 
was  modified  as  to  appetite,  sleep,  color,  weight,  or  strength  in 
70  per  cent,  of  cases.  Mental  attitude  was  favorably  modified 
in  71  per  cent,  of  cases.  The  condition  of  the  cancer  mass  itself 
was  favorably  modified  in  69  per  cent,  of  cases,  with  marked 
regression  in  size  in  27  per  cent. 

In  reporting  these  results  to  a  professional  audience,  I  added 
this  comment:  "Dealing,  as  the  statistics  do,  with  supposedly 
hopeless  cases,  in  the  presence  of  which  the  physician  has  hith- 
erto stood  powerless,  and  with  symptoms  mostly  not  susceptible 
of  amelioration  by  any  agency  hitherto  available,  this  is  a  showing 
at  once  amazing  and  enheartening." 

A  few  months  later  I  was  able  to  establish  the  important 
new  principle  that  it  is  not  possible  to  get  cumulative  and  opti- 
mum results  from  the  use  of  a  single  protein  or  combination  of 
proteins,  inasmuch  as  the  system  develops  a  degree  of  immuniza- 
tion. It  was  found  that  a  case  that  had  become  static,  after 
a  period  of  progress,  might  take  on  a  new  response  when  a 
new  type  of  protein  was  administered.  This  principle  has  been 
borne  constantly  in  mind  in  my  personal  use  of  the  Proteal  treat- 
ment, and  I  have  inculcated  it  persistently  in  advising  with  asso- 
ciated physicians.  Perhaps  it  will  be  of  interest  to  reproduce 
here  a  brief  history  of  the  patient  upon  whom  the  experience  of 
shifting  from  one  type  of  protein  to  another  was  first  made : 

Case  of  Mrs.  V.  Cancer  of  the  left  breast  removed  by  sur- 
geon in  September,  1915.  Recurrence  above  the  clavicle  and 
about  the  neck ;  pronounced  inoperable.  Non-specific  protein 
treatment  (hypodermically  into  the  upper  arm)  begun  in  Sep- 
tember, 1915.  Striking  modification  of  the  blood,  steady  im- 
provement of  general  condition,  and  fairly  rapid  regression  of 
the  cancerous  mass.  In  June,  1916,  only  a  few  small  enlarge- 
ments remained,  but  these  appeared  to  be  static.  A  new  Proteal, 
extracted  from  alfalfa  seed,  was  administered,  and  the  masses 
at  once  regressed,  until  only  a  single  gland,  as  large  as  the  little 
finger-nail,  was  observable  just  above  the  clavicle.  This  was 
excised  with  local  anaesthesia,  the  incision  healing  promptly. 
Occasional  doses  of  Proteal  were  given  at  lengthening  intervals, 
and  the  patient  is  still  under  observation ;  but  she  has  been  to  all 
appearance  perfectly  well  for  the  past  eighteen  months.  She 
is  of  normal  weight  and  appearance;  does  housework  energeti- 
cally; reports  herself  as  feeling  as  well  and  as  strong  as  ever 
in  her  life.  This,  it  will  be  observed,  two  years  after  the  case 
had  been  pronounced  hopeless  by  the  surgeons,  the  diagnosis 
of  cancer  of  malignant  type  having  been  confirmed  with  the 
microscope. 


172      THE   PROTEOMORPHIC  THEORY   AND  THE   NEW   MEDICINE 

The  value  of  a  shift  from  one  Proteal  to  another,  illustrated 
by  the  above  case,  has  been  demonstrated  over  and  over.  Many 
types  of  vegetable  proteins  are  now  extracted  in  my  laboratory, 
and  new  ones  are  constantly  being  tested.  It  is  routine  practice 
to  shift  from  one  Proteal  to  another  in  the  treatment  of  any 
intractable  case.  To  a  large  extent  the  different  vegetable  pro- 
teins are  interchangeable,  but  no  single  one  can  produce  optimum 
results  unaided. 

As  illustrating  the  possibilities  of  the  Proteal  method  in  its 
present  state  of  development,  I  may  cite  the  history  of  a  case 
even  more  striking  than  the  one  just  presented : 

Case  of  Mr.  F.  Carcinoma  of  the  stomach.  Operated  on  in 
September,  1916,  by  surgeons  in  Cincinnati,  who  found  a  can- 
cerous mass  completely  filling  the  pyloric  end  of  the  stomach 
and  involving  the  liver.  No  attempt  made  to  remove  the  mass, 
but  an  opening  was  made  in  the  front  side  of  the  stomach  and 
the  intestine  attached  to  permit  passage  of  food.  The  case  was 
regarded  as  absolutely  hopeless.  The  patient  came  to  me  for 
Proteal  treatment  five  months  later,  February  25,  1917,  in  des- 
perate condition,  regarded  by  his  friends  and  physicians  as  be- 
yond the  reach  of  medication.  The  response  to  Proteal  treat- 
ment (administered  hypodermically  into  the  back  of  the  upper 
arm)  was  immediate.  Rapid  transformation  took  place  in  the 
blood  conditions,  appetite  improved,  and  the  capacity  to  assimi- 
late food.  Strength  was  gained  from  day  to  day.  Painful  swell- 
ings of  the  knee  joints,  which  had  been  a  distressing  complica- 
tion, disappeared.  The  cancer  mass  in  the  abdomen,  which  could 
be  readily  felt  through  the  emaciated  abdominal  wall,  decreased 
rapidly  in  size  until  it  was  not  more  than  one-fourth  its  original 
dimensions.  For  a  time  the  patient  did  not  gain  weight;  then 
he  began  gradually  and  steadily  to  gain,  and  in  nine  months  he 
had  put  on  twenty  pounds.  When  the  treatment  was  begun  in 
February,  the  patient  did  not  attempt  to  leave  the  house  unat- 
tended. Eight  months  later  he  made  a  trip  by  himself  from 
New  York  to  his  old  home  in  Cincinnati  to  attend  a  banquet, 
participating  actively  in  all  the  festivities  associated  with  the 
event,  and  reporting  himself,  after  returning  to  New  York,  as 
feeling  in  tip-top  condition.  He  was  received  by  his  old  friends 
and  associates  almost  as  one  risen  from  the  dead.  Whatever  the 
future  progress  of  his  case,  there  can  be  little  question  that  the 
life  of  this  patient  has  been  extended  by  many  months  solely  by 
Proteal  treatment. 

To  show  that  similar  results  may  be  attained^by  physicians  who 
have  had  comparatively  slight  experience  with  the  Proteals,  I 
may  cite  a  very  brief  report  from  a  physician  in  the  North- 


THE  SCIENCE   AND  ART  OF   PROTEAL  THERAPY  173 

west,  that  chances  to  come  to  me  just  as  I  am  writing  this 
article : 

"Mrs.  A.  O.  Age  53.  Cancer  of  the  stomach.  Small  tumor 
at  pyloric  size  of  walnut.  Under  Proteal  treatment  tumor  Dis- 
appeared. Stomach  symptoms  (nausea,  vomiting,  pain)  dis- 
appeared. No  more  blood  discharges.  Blood  picture  improved. 
Strength  and  general  condition  improving." 

It  will  be  observed  that  I  have  not  used  the  word  cure  in 
connection  with  the  Proteal  treatment  of  cancer.  The  word 
cure  is  one  that  I  shall  not  use  until  at  least  five  years  have 
elapsed  after  the  clinical  recovery  of  a  cancer  case.  I  am  hope- 
ful, however,  that  ultimately  such  reports  may  be  possible.  This 
hope  finds  justification  in  the  fact  that  some  of  the  cases  that 
have  been  longest  under  treatment  have  shown  no  tendency  to 
recurrence.  Here,  for  example,  is  the  record  of  a  case  treated 
by  Dr.  E.  H.  Williams,  of  Los  Angeles,  and  reported  by  him  in 
the  New  York  Medical  Journal  of  October  9,  1915. 

Patient  with  recurrent  inoperable  cancer  of  the  neck.  Treat- 
ment begun  in  June,  1915.  Patient  made  spectacular  progress 
under  hypodermic  treatment,  the  cancer  mass  regressing  rapidly 
and  altogether  disappearing  in  less  than  a  month.  The  patient 
has  now  had  no  treatment  whatever  for  more  than  two  and  a 
half  years,  and  he  continues  in  apparently  perfect  health.  There 
has  been  no  tendency  to  return  of  the  cancer,  and  no  manifes- 
tation of  abnormality  of  any  kind. 

On  the  day  on  which  the  copy  for  this  chapter  goes  to  the 
printer,  a  letter  comes  to  me  from  physician  number  746  (my 
office  files),  of  New  Hampshire,  telling  of  a  cancer  patient,  a 
woman,  treated  by  him  so  effectively  with  the  Proteals  (No.  45) 
that  in  October,  1917,  she  was  "in  fair  health  and  strength,  and 
able  to  do  very  good  work  in  an  eating  saloon,  acting  as  table 
girl,"  with  "no  evidence  of  cancer  about  her  system,"  and  now, 
having  found  the  work  of  lifting  the  waiters  too  heavy,  she  is 
occupied  regularly  in  a  factory,  and  has  gained  fifteen  pounds 
in  weight,  is  of  good  color,  and  seemingly  well. 

With  such  reports  as  this  coming  from  physicians  in  various 
parts  of  the  world,  many  of  whom  are  quite  unknown  to  me 
personally,  to  fortify  my  individual  observations,  I  feel  amply 
justified  in  reiterating  the  statement  that  the  results  of  the 
Proteal  treatment  of  cancer  are  in  the  highest  degree  encour- 
aging and  enheartening.  It  would  certainly  seem  within  bounds 
to  say  that  the  Proteal  method  offers  new  hope  for  cancer 
sufferers  everywhere  in  the  world. 

In  some  of  my  addresses  to  companies  of  fellow-physicians 
I  have  gone  a  step  further,  venturing  the  prediction  that  Pro- 
teal  treatment  will  in  the  immediate  future  assauge  far  more 


174      THE   PROTEOMORPHIC  THEORY   AND  THE   NEW    MEDICINE 

suffering  than  the  world  war  causes,  and  will  within  the  pres- 
ent generation  save  ten  lives  for  every  one  that  the  war  exacts. 

PROTEAL  THERAPY  AND  RHEUMATOID  CONDITIONS 

Through  circumstances  with  which  the  reader  of  earlier  parts 
of  this  volume  is  familiar,  the  original  proteal  extracts  were  at 
first  administered  solely  to  cases  of  inoperable  cancer.  But  it 
was  inevitable  that  any  one  who  thoughtfully  regarded  the  ob- 
served results  of  this  treatment — noting  in  particular  the  blood 
modifications — should  question  presently  whether  maladies  of 
kindred  origin  might  not  fall  within  the  scope  of  the  protein 
treatment. 

At  a  very  early  day  I  suggested  the  possibility  that  a  remedy 
producing  such  striking  modifications  of  the  blood  should  be 
applicable  to  the  wide  range  of  affections,  bacterial  and  other- 
wise, associated  with  modifications  of  the  blood  count.  It  was 
agreed  that  tests  as  to  this  might  advantageously  be  made  as  soon 
as  experience  was  well  grounded. 

It  chanced,  however,  that  the  observations  tending  to  confirm 
the  opinion  that  the  proteal  extract  might  have  wider  application 
were  made  by  a  New  York  physician  quite  by  accident.  Among 
the  patients  that  came  for  treatment  while  the  protein  method 
was  still  in  its  infancy  was  a  woman  with  cancer  of  the  breast, 
who  also  suffered  from  a  severe  arthritis  of  many  years'  standing. 

A  published  account  of  this  case  has  described  the  condition 
of  the  patient  before  treatment  as  follows : 

"The  arthritis  had  affected  the  joints  of  the  hands,  wrists, 
elbows  and  ankles.  The  patient  had  had  a  variety  of  treatment 
without  effect  and  suffered  at  the  time  when  she  was  first  seen 
more  from  the  pain  of  the  arthritis  than  from  the  recurrence  of 
the  malignant  growth.  The  joints  of  the  hands  showed  the  most 
deformity,  there  was  a  typical  ulnar  deflection,  the  articular  sur- 
faces were  enlarged  and  in  some  joints  eroded,  the  hands  could 
not  be  used  for  any  useful  purpose,  there  were  frequent  exacer- 
bations accompanied  by  increased  swelling  and  redness  of  the 
joints  and  increased  pain.  The  affected  joints  served,  in  fact, 
as  so  many  of  them  do,  as  a  barometer  of  the  weather  con- 
ditions." 

The  case  is  not  the  less  interesting  because,  as  already  noted, 
the  treatment  was  aimed  entirely  at  the  relief  of  the  returned 
cancer  of  the  breast,  with  no  thought,  originally,  that  the  rheu- 
matic condition  would  be  in  any  way  affected.  The  treatment, 
aside  from  general  hygienic  precautions,  consisted  exclusively 
of  the  hypodermic  administration  of  the  original  proteal  ex- 
tract. Note  now  the  sequel : 


THE   SCIENCE   AND  ART  OF  PROTEAL  THERAPY  175 

"At  the  time  the  patient  began  the  treatment  she  could  not 
use  her  hands  for  any  purpose  and  walked  with  difficulty.  The 
injections  were  administered  every  second  day  in  gradually  in- 
creasing doses,  beginning  with  ten  minims.  During  the  course 
of  the  first  three  weeks  they  were  increased  to  twenty  minims. 
At  this  time  my  attention  was  called  by  the  patient  to  the  fact 
that  she  now  used  her  hands,  for  the  past  week  had  practically 
no  pain,  was  able  to  button  her  clothing  and  was  relieved  of  the 
discomforts  of  the  disease  to  a  degree  which  she  had  not  experi- 
enced in  years.  This  improvement  continued  so  that  from  this 
time  on  the  patient  practically  suffered  no  more  pain  from  the 
diseased  joints.  The  use  of  the  hands  gradually  returned  so 
that  she  was  able  to  write,  she  could  use  a  needle  for  sewing 
and,  while  the  bony  changes  were  in  no  way  influenced,  the 
surrounding  inflammatory  swelling  did  decrease  and  she  con- 
tinued in  comparative  comfort." 

The  observer  was  naturally  impressed  by  these  changes  in  the 
joint  conditions,  and  he  was  quite  unable  to  explain  them  except 
upon  the  basis  of  the  effect  produced  by  the  protein  medication. 
Very  naturally,  he  recalled  the  circumstances  of  this  case  when  a 
second  patient  who  was  suffering  from  a  rather  rapid  develop- 
ment of  arthritis  of  similar  character  came  under  his  observation. 
This  patient  was  a  woman  36  years  of  age.  The  history  of  her 
disease  extended  over  a  period  of  two  years,  the  joints  involved 
being  those  of  the  hand,  wrists,  elbows,  ankles,  and  knees.  The 
patient  had  suffered  intense  pain. 

The  condition  of  this  patient  before  treatment  is  described  as 
follows : 

"The  bony  changes  were  not  as  pronounced  as  in  the  case 
of  the  first  patient,  but  the  development  had  been  .more  acute, 
the  history  extending  over  a  period  of  approximately  two  years. 
She  had  already  passed  through  the  hands  of  several  physi- 
cians who  had  employed  various  therapeutic  measures,  including 
careful  dieting  and  observation  of  the  gastro-intestinal  tract, 
vaccination  from  cultures  obtained  from  the  teeth  and  a  further 
course  of  vaccination  with  a  mixed  vaccine  originated  by 
Schaefer.  The  combined  vaccines  of  Schaefer  had  given  some 
relief,  but  had  produced  violent  constitutional  reactions  which 
had  been  unfavorable  to  the  general  health  of  the  patient.  At 
the  time  of  her  first  visit  she  was  suffering  so  intensely  that 
she  could  not  walk  and  was  carried  into  my  office.  I  could  not 
find  a  source  of  infection  that  seemed  adequate  to  explain  the 
difficulty." 

This  patient  was  at  first  treated  by  regulating  of  diet  and  atten- 
tion to  general  hygiene,  together  with  the  administration  of  thy- 
roid and  thymus  extracts.  In  the  course  of  one  month  some  mild 


176      THE   PROTEOMORPHIC   THEORY  AND  THE    NEW    MEDICINE 

improvement  had  resulted  from  these  measures.  Then  the  strik- 
ing changes  observed  in  the  first  patient,  as  above  noted,  led  to 
the  decision  to  administer  the  Proteal  treatment  in  this  second 
arthritis  case,  although  the  treatment  had  theretofore  been  ap- 
plied solely  to  patients  suffering  from  cancer.  The  administration 
of  the  Proteal  extract  was  begun  on  the  28th  of  May,  1915. 

The  injections  were  continued  over  a  period  of  nine  months. 
At  the  outset  the  patient  had  been  taking  40  to  60  grains  of 
aspirin  each  twenty-four  hours  to  relieve  the  pain.  The  amount 
was  promptly  diminished  in  the  course  of  the  first  three  weeks 
of  the  Proteal  treatment,  and  in  the  course  of  two  months  the 
drug  was  entirely  discontinued. 

Here  is  the  report  on  the  treatment  and  its  results: 

"During  the  earlier  months  of  the  treatment  the  injections 
were  given  every  second  day,  during  the  last  four  months  the 
interval  between  the  injections  was  gradually  increased  until 
finally  an  injection  was  given  only  once  a  week.  The  patient's 
improvement  was  gradual  but  definite,  and  she  finally  reached 
and  maintained  a  state  of  health  satisfactory  in  every  respect. 
The  bony  changes  about  the  affected  joints  have  never  been  re- 
lieved and  it  seems  very  doubtful  if  they  ever  will  be.  How- 
ever, the  infiltration  and  thickening  of  the  soft  tissues  has  been 
entirely  relieved.  During  the  past  six  months  this  patient  has 
had  no  treatment  whatever.  She  has  been  in  excellent  health, 
has  gained  twenty- four  pounds  in  weight  during  the  course  of 
the  treatment,  and  during  the  past  summer  has  been  unusually 
active,  playing  tennis,  swimming  and  doing  a  variety  of  house- 
hold work,  using  her  hands  with  perfect  freedom  and  comfort 
for  such  mechanical  operations  as  writing,  fine  sewing,  etc." 

The  clinical  progress  of  this  case  was  matched  by  the  modi- 
fications in  the  blood  conditions.  Starting  with  a  red  blood 
count  of  a  little  over  two  million  and  hemaglobin  of  70  per  cent., 
the  records  show  that  on  the  17th  of  September  the  red  blood 
count  was  3,900,000,  the  hemaglobin  79  per  cent.  On  the  14th 
of  December  the  red  count  was  4,444,000,  the  white  count  6,700, 
the  hemaglobin  90  to  95  per  cent.  On  the  27th  of  December  the 
red  corpuscles  numbered  5,280,000,  the  white  corpuscles  8,000. 
The  differential  count,  at  a  time  when  the  treatment  was  most 
actively  pursued,  showed  53  per  cent,  polynuclears,  25.5  per 
cent,  large  monocytes,  12  per  cent,  small  lymphocytes,  and  9.5 
per  cent,  eosinophiles.  At  a  later  date  (December  27th),  when 
the  patient  was  receiving  only  weekly  Proteal  treatment,  the  dif- 
ferential count  showed  polynuclears,  14.5  per  cent,  large  mono- 
cytes, 22.5  per  cent,  small  lymphocytes,  and  3  per  cent,  eosino- 
philes. 

It  is  significant  that  two  years  have  now  elapsed  since  treat- 


THE   SCIENCE   AND  ART   OF   PROTEAL  THERAPY  177 

ment  was  discontinued  in  the  case  under  consideration,  and 
that  the  patient  remains  in  a  condition  of  normal  health.  She 
was  under  treatment  for  hay  fever  for  a  short  time  during  the 
summer  following  the  disappearance  of  her  rheumatoid  difficul- 
ties, but  there  has  been  no  evidence  of  a  tendency  to  recurrence 
of  the  old  malady. 

In  recent  months  a  number  of  cases  of  arthritis  of  various 
types  have  come  under  treatment  in  my  office.  Reports  have 
come  to  me  also  from  other  physicians  who  have  used  the  Pro- 
teals  from  my  laboratory  in  the  treatment  in  cases  of  rheuma- 
tism of  various  types.  The  evidence  as  a  whole  is  not  yet  in 
any  wise  comparable  to  the  evidence  regarding  the  Proteal  treat- 
ment of  cancer,  but  in  the  main  it  is  corroborative  of  the  observa- 
tions above  recorded.  Patients  suffering  from  the  most  intract- 
able forms  of  arthritis  have  had  their  pains  banished  and  their 
rigid  joints  made  mobile.  Patients  suffering  from  milder  types 
of  rheumatism  have  shown  amelioration  of  the  unpleasant  symp- 
toms and  conspicuous  improvement  in  the  general  condition — 
together  with  a  characteristic  regenerative  modification  of  the 
blood — almost  from  the  outset.  With  cases  of  the  latter  type 
doses  of  5  to  10  minims  of  one  of  the  standard  Proteal  extracts 
— for  example,  No.  45 — have  proved  efficacious.  For  the  more 
severe  cases  the  dosage  has  been  advanced,  gradually,  to  15,  20, 
and  even  30  minims.  But  I  have  not  thought  it  necessary  or 
desirable  to  force  the  dosage  to  the  point  of  producing  severe 
reactions  as  a  rule.  I  believe  the  best  results  are  attainable  by 
giving  relatively  small  doses  for  a  long  period  of  time. 

Spectacular  results  through  the  use  of  one  or  two  heroic  doses 
have  been  reported  in  recent  months  by  physicians  using  the 
proteins  of  the  typhoid  bacillus ;  but  it  is  my  opinion  that  the 
method  designed  to  bring  about  slow  and  gradual  modifications 
in  the  affected  joints  will  be  found  in  the  end  more  efficacious, 
as  it  is  unquestionably  the  more  pleasant  method  of  treatment. 

Details  of  technique  aside,  -however,  it  would  appear  that  the 
evidence  justifies  a  large  measure  of  confidence  in  the  possibili- 
ties of  treating  rheumatsm  and  various  rheumatoid  conditions 
with  non-specific  proteins — associated,  as  a  matter  of  course, 
with  general  hygienic  measures,  including  low  protein  (and 
chiefly  vegetable  protein)  diet  and  systematic  exercises. 

DIETETIC  ANOMALIES  EXPLAINED 

As  to  diet,  however,  I  would  offer  a  suggestion,  which  will 
perhaps  seem  anomalous ;  but  which  is  based  on  a  wide  range  of 
experience  in  the  first  instance,  and  supported  theoretically  by 
the  fundamental  principles  of  the  Proteomorphic  theory.  It 


178      THE   PROTEOMORPHIC  THEORY   AND  THE    NEW    MEDICINE 

is  to  the  effect  that,  whereas  I  advocate  a  low  protein  diet  for 
people  at  middle  age  and  later,  in  health  and  in  toxaemic  mala- 
dies, and  in  particular  a  low  animal  protein  diet,  with  emphasis 
on  the  exclusion  of  bearers  of  purin-bases  for  rheumatoid  cases, 
I  nevertheless  believe  it  advantageous  occasionally  to  permit  the 
patient  to  depart  from  the  rule  and  indulge  in  a  meal  including 
a  moderate  portion  of  meat — for  example,  about  three  cubic 
inches  of  beefsteak. 

It  is  a  familiar  experience  that  such  a  meal,  indulged  by 
exception  and  not  too  frequently,  has  a  stimulative  or  tonic 
effect.  Haig  explains  this,  as  will  be  recalled  by  every  one 
familiar  with  his  oft-berated  but  never  discredited  work  on  Uric 
Acid,  on  the  assumption  that  the  beef  tends  to  acidify  the  liver 
and  cause  that  organ  to  sieve  the  uric  acid  out  of  the  blood 
temporarily — an  explanation  that  appears  to  me  altogether  fan- 
ciful and  fallacious.  Doubtless  my  own  explanation  will  seem 
equally  fanciful  to  any  one  who  has  not  grasped,  or  does  not 
accept,  the  fundamental  thesis  of  the  Proteomorphic  theory. 
Be  that  as  it  may,  my  explanation  is  that  a  certain  amount  of 
the  protein  of  the  steak  is  pretty  sure  to  find  its  way  into  the 
parenteral  system  not  fully  decompounded  (experiments  cited 
in  earlier  chapters  fully  warrant  this  assumption),  and  will  thus 
act  as  a  proteantigen  stimulating  corpuscular  response  precisely 
as  if  it  had  been  introduced  hypodermically.  In  effect,  eating 
the  steak  was  equivalent  to  giving  treatment  with  a  protein  of  a 
type  which  is  not  familiar  (since  the  meat  is  eaten  only  at  rather 
long  intervals),  and  against  which  the  system  is  not  at  the  moment 
fully  immunized. 

The  corpuscular  response  includes,  according  to  hypothesis, 
increased  enzymic  activities  of  the  corpuscles ;  enhancing,  there- 
fore, the  purin-body-reducing  functions  of  the  erythrocytes, 
and  thus  tending  to  clear  the  blood  of  uric  acid — in  accordance 
with  Haig's  statement  of  the  fact,  but  not  at  all  in  accordance 
with  his  explanation  of  the  modus  operandi.  The  increased 
activity  of  the  red  corpuscles  and  their  consequent  excessive 
destruction  in  the  liver  might  indeed  be  said  to  "acidify"  that 
organ,  through  increased  influx  of  uric  acid,  and  in  particular 
urea,  from  the  bodies  of  the  disrupted  erythrocytes;  but  the 
"sieving"  process,  according  to  the  present  thesis,  would  consist 
in  the  increased  capacity  of  the  erythrocytes  to  transform  uric 
acid  into  urea  (see  Chapter  I  above). 

Meantime,  of  course,  the  beef  protein  ingested,  if  entering 
the  parenteral  system  more  or  less  fully  digested,  but  short  of 
the  amino-acid  stage,  would  bring  an  increment  of  purin  bodies 
that  would  add  to  the  uric  acid  supply.  Where  the  balance 
would  be  struck,  in  any  individual  case,  would  depend  upon  the 


THE   SCIENCE   AND  ART  OF   PROTEAL  THERAPY  179 

quantity  of  meat  ingested  and  the  length  of  time  that  had  elapsed 
since  the  organism  had  been  habitually  invaded  by  this  partic- 
ular protein.  It  is  consonant  with  the  Proteomorphic  concep- 
tion to  assume  that  even  when  the  beef  protein-products  entered 
the  blood  at  the  polypeptid  stage,  they  would  act  as  antigens 
directly  stimulating  the  mother-cells  of  the  erythrocytes  and  the 
enzymic  response  of  the  erythrocytes  themselves — provided  al- 
ways that  these  cells  were  not  sated  by  habitual  presence  of 
these  particular  proteins. 

Should  intestinal  digestion  be  so  perfect  that  all  the  beef  pro- 
tein is  reduced  to  the  amino-acid  stage  before  passing  into  the 
parenteral  system,  there  would  no  such  antigenic  effect — nor, 
in  all  probability,  would  purin  bodies  be  included;  but  there  is 
reason  to  believe  that  enteric  digestion  seldom  is  so  perfect  as 
this — particularly  in  case  of  persons  of  rheumatoid  diathesis, 
since  they,  almost  by  definition,  suffer  from  intestinal  toxaemia. 
Indeed,  as  was  earlier  pointed  out,  it  is  not  quite  certain  that 
the  proteins  do  not  normally  enter  the  blood  as  polypeptids. 

Such,  then,  is  the  theoretical  reasoning  through  which  I  find 
warrant  for  the  practice  of  admonishing  my  patients — rheuma- 
toid, anaemic,  cancerous,  tubercular — to  regard  an  occasional,  but 
not  too  frequent,  infraction  of  the  purin-free  diet  rule  as  a 
part  of  the  rule.  The  radical  distinction  between  such  occasional 
indulgence  and  habitual  ingestion  of  the  purin-bearing  proteins 
will  be  obvious  to  any  one  who  recalls  the  oft-reiterated  prin- 
ciple that  an  incessant  stimulus  from  the  constant  invasion  of  a 
protein  of  any  type  leads  to  the  corpuscular  exhaustion  implied 
in  what  has  been  repeatedly  spoken  of  (though  perhaps  the 
phrase  in  this  connection  is  not  very  defensible)  as  immunization 
to  the  effects  of  a  given  protein. 

Incidentally  it  may  be  noted  that  the  utter  satiety  that  attends 
the  too  continuous  ingestion  of  a  single  type  of  foodstuffs  is  thus 
to  be  explained.  So  far  as  I  am  aware,  no  other  really  intelligible 
explanation  of  this  anomaly  has  hitherto  been  forthcoming.  The 
oft-cited  paradox  (doubtless  not  literally  true,  yet  symbolizing 
a  profound  dietetic  truth)  that  no  one  can  eat  a  quail  a  day 
for  thirty  days  without  utter  satiety,  thus  finds  scientific  elu- 
cidation, 

PROTEALS  IN  THE  HANDS  OF  THE  PRACTITIONER 

All  this,  however,  is  carrying  us  afield  from  the  question  of 
the  treatment  of  rheumatoid  conditions  with  Proteals — though, 
after  all,  not  far  afield,  as  will  appear  when  an  explanation  of 
the  action  of  the  Proteals  in  this  connection  is  given  a  little 
later.  First,  however,  it  will  be  well,  as  establishing  the  prac- 


180      THE   PROTEOMORPHIC  THEORY   AND  THE   NEW    MEDICINE 

tical  status  of  the  Proteals  in  the  matter,  to  cite  a  few  individual 
experiences  of  physicians  using  Proteals  from  my  laboratory  in 
the  treatment  of  familiar  types  of  chronic  arthritis.  Here,  for 
example,  is  an  informal  letter  from  physician  number  726  (ac- 
cording to  my  office  files),  of  Oregon: 

"Mr.  F.  was  the  first  case  treated  by  me.  Had  been  stiff  and 
unable  to  walk  for  several  years.  Nervous  system  run  down. 
Administered  doses  as  per  directions.  Noted  improvement  in 
three  weeks'  time.  Health  generally  better;  strength  returning. 
A  maximum  dose  of  twenty-four  minims  [of  Proteal  No.  45] 
three  times  with  good  results.  Gave  him  injections  daily.  Now 
he  is  able  to  walk  without  crutches  with  the  assistance  of  some 
one  to  steady  him."  The  treatment  was  given  in  association 
with  the  use  of  an  electric  baking  apparatus. 

Of  similar  tenor  is  a  letter  from  physician  number  232  (new 
series),  of  Arkansas: 

"The  hands — which  were  contracted  so  she  could  not  extend 
them  and  could  barely  get  a  staff  into  each  hand  for  walking — 
and  the  feet  and  hips  were  so  stiff  and  sore  she  could  not  stand 
or  move  except  with  the  twa  staffs  in  hand.  She  can  now  ex- 
tend fingers,  pain  almost  gone,  and  walks  upright  and  has  thrown 
away  the  sticks." 

A  little  later  the  same  physician  made  a  brief  formal  report 
on  his  first  four  arthritis  cases  under  Proteal  treatment,  which 
has  added  interest  because  the  type  of  Proteal  and  the  dosage 
employed  in  each  case  are  specified: 

Case  1. — Male  age  60.  Rheumatism  of  wrists  and  finger  joints. 
Pain  at  night  of  an  aching  character  causing  considerable  loss 
of  sleep.  These  pains  had  been  persistent  and  increasing  for  10 
years.  Treatment  began  with  six  minims  of  mixed  Proteals 
[No.  45 — proteins  of  alfalfa  seed,  alfalfa  meal,  and  millet  seed] 
every  other  day,  subcutaneously  in  forearms,  increased  injec- 
tions gradually  to  twenty  minims.  Ten  treatments  given  and  cure 
resulted.  No  general  reaction,  but  there  was  a  marked  local 
reaction  with  itching  and  stinging  and  marked  cutis  anserinus 
of  about  two  inches  surrounding  the  site  of  each  injection  that 
persisted  about  three  days  each  time. 

Case  2. — Rheumatic  arthritis.  Male  age  58.  Disease  affects 
hands,  elbows,  shoulders,  and  hips.  Could  walk  with  difficulty 
by  means  of  two  staffs,  one  in  each  hand.  Could  barely  open 
hands  sufficiently  to  get  staff  (one  inch  in  diameter)  into  hands. 
Tendons  badly  drawn  and  joints  enlarged  and  very  tender. 
Began  treatment  with  six  minims  of  mixed  Proteals  [No.  45, 
as  above]  every  other  day.  No  general  reaction,  slight  local 
reaction.  Increased  the  Proteals  gradually  to  twenty  minims. 
Gave  in  all  twelve  treatments,  with  marked  improvement  in  all 


THE   SCIENCE  AND  ART   OF   PROTEAL  THERAPY  181 

joints,  At  close  of  last  treatment  patient  could  walk  fairly  well 
without  any  staffs  and  could  open  hands  three-quarters  of  nor- 
mal extension.  This  patient  left  the  city  and  must  be  improving 
yet  or  he  would  report  to  me. 

Case  3. — Mr.  S.  Age  48.  Rheumatism  of  the  fingers  with 
deposits  about  joints,  particularly  about  last  joint  of  right  index 
ringer,  to  such  an  extent  he  could  flex  the  finger  but  a  trifle 
owing  to  a  lump  on  under  and  outer  side  of  the  joint.  Six  to 
sixteen  minims  of  mixed  Proteals  [No.  45]  gave  slow  improve- 
ment until  we  were  halted  by  a  serious  abscess  at  site  of  one 
injection.  A  rest  of  four  weeks  and  then  six  injections  of  the 
rape  seed  Proteal  [No.  42]  on  alternate  days  caused  improve- 
ment sufficient  for  him  to  almost  completely  flex  index  finger. 
He  is  in  much  better  health  and  comfort  and  frankly  attributes 
relief  to  the  treatment. 

Case  4. — Mrs.  M.  Age  44.  Chronic  articular  rheumatism  of 
four  years'  duration,  in  feet  and  ankles,  knees,  hips,  fingers, 
wrists,  elbows,  and  shoulders.  Had  been  bedfast  several  times ; 
never  much  improvement.  Suffered  greatly  with  soreness,  swell- 
ing, and  tenderness  of  joints.  Began  with  six  minims  of  rape 
Proteal  [No.  42],  subcutaneously.  Ached  and  hurt  all  night 
following  first  injection.  Continued  and  increased  the  treatment 
every  other  day  for  two  weeks,  with  steady  improvement  and 
no  further  reactions.  After  three  weeks  the  improvement  ceased 
and  I  changed  to  fifteen  minims  of  alfalfa  seed  Proteal  [No. 
39].  A  very  marked  improvement  followed.  Increased  the  al- 
falfa gradually  to  25  minims.  Four  alfalfa  injections  were  given, 
when  she  seemed  almost  entirely  cured.  At  this  time  her  son 
and  husband  were  stricken  with  typhoid  fever.  She  nursed  and 
cared  for  both,  until  the  husband  died.  During  the  four  weeks 
of  this  unusual  strain,  she  showed  no  return  of  the  trouble, 
but  to-day  she  returned  with  the  report  that  she  begins  to  have 
pains  in  the  feet,  ankles,  and  knees  and  they  are  somewhat 
swollen,  and  I  have  resumed  alfalfa,  10  minims. 

As  representing  an  initial  experience  with  Proteal  therapy, 
this  record  of  marked  improvement  of  four  consecutive  cases  of 
intractable  character  in  the  hands  of  a  single  practitioner  is 
certainly  enheartening.  The  aggregate  number  of  such  reports, 
giving  tangible  support  to  my  personal  experiences,  is  already 
notable.  But  in  particular  there  come  to  me  day  by  day  informal 
letters  from  associated  physicians  that  are  often  more  stimulative 
than  formal  reports.  For  example,  here  is  one  that  came  to 
hand  in  this  morning's  mail  from  a  physician  out  in  North 
Dakota,  with  reference  to  a  typical  case  of  rheumatoid  arthritis 
that  has  been  under  Proteal  treatment  for  eight  months. 

"Mrs.  —  feels  that  the  Proteal  treatment  is  helping  her,  and 


182      THE   PROTEOMORPHIC   THEORY   AND  THE   NEW    MEDICINE 

I  can  see  an  improvement,  although  the  affected  joints  are  still 
stiffened  and  sore.  She  rests  much  better  and  has  not  the  con- 
stant pain  that  bothered  her  so  much  formerly.  She  is  enthu- 
siastic, and  wishes  to  keep  up  the  treatment  faithfully." 

Another  recent  letter,  this  time  from  British  Columbia,  tells 
that  the  patient,  for  fifteen  years  a  sufferer  from  rheumatoid 
arthritis  of  the  most  intractable  type,  has  just  stood  upon  her 
feet  for  the  first  time  in  ten  months,  and  has  found  a  measure  of 
relief  from  pain  under  Proteal  treatment  after  she  had  long 
despaired  of  ever  finding  solace. 

I  would  not  be  understood  to  imply,  however,  that  Proteal 
therapy  has  hitherto  proved  adequate  or  satisfactory  in  all  rheu- 
matoid cases  to  which  it  has  been  applied.  I  have  seen  it  fail 
in  at  least  one  case  that  came  under  my  personal  observation. 
The  patient  is  a  case  of  chronic  arthritis,  of  progressive  type, 
who  twice  came  to  my  office  for  personal  examination,  and  to 
whom  the  Proteals  were  administered  in  varying  dosage  for  a 
term  of  months.  On  the  morning  on  which  I  am  completing  this 
chapter,  I  received  (from  physician  number  767,  New  York) 
the  following  letter: 

"I  regret  to  report  that  Mrs.  —  does  not  show  any  improve- 
ment under  treatment  with  Proteals;  I  cannot  conscientiously 
say  there  has  been  relief  in  any  of  the  joints,  while  the  cervical 
and  lumbar  vertebrae  seem  now  to  be  involved.  It  is  certainly 
an  obstinate  infirmity.  Apparently  in  this  particular  case  the 
Proteal  does  not  seem  to  have  developed  any  protection." 

I  may  add  that  earlier  reports  suggest  a  certain  improvement 
in  general  health,  which,  however,  was  not  of  vast  significance ; 
and  that  there  were  modifications  of  the  blood  count  that  led 
at  one  time  to  favorable  anticipations.  But  apparently  in  this 
case  we  have  failed  hitherto  to  find  the  source  of  disturbed  meta- 
bolism or  to  counteract  effectively  the  pre-existing  maladjust- 
ments. 

In  the  contrast  with  this  unsatisfactory  showing,  I  may  quote 
a  letter  from  another  physician  concerning  a  case  that  also  had 
come  under  my  personal  observation,  but  which,  like  the  case 
just  cited,  was  not  treated  personally  by  me,  although  in  both 
cases  the  Proteals  used  were  supplied  from  my  laboratory.  Here 
is  the  letter  (from  physician  number  784,  Montana)  : 

"The  patient  whom  you  saw  when  you  were  lecturing  on  the 
Chautauqua  Circuit  has  shown  a  remarkable  improvement.  All 
his  friends  speak  about  his  ease  in  walking.  Perhaps  you  do  not 
recall,  but  he  was  suffering  from  chronic  arthritis,  and  of  some 
of  the  notables  who  treated  him,  Dr.  —  [a  famous  Chicago 
physician]  was  the  last.  The  patient  has  attended  two  dances 
and  taken  an  active  part  since  beginning  the  Proteal  treatment." 


THE   SCIENCE   AND  ART  OF   PROTEAL  THERAPY  183 

This  patient,  when  I  saw  him,  in  August,  1917,  did  not  attempt 
to  rise  from  his  chair.  His  arthritic  involvement  had  been 
progressive,  and  had  resisted  all  the  conventional  lines  of  treat- 
ment, including  vapor  and  mud  baths,  change  of  climate,  removal 
of  the  tonsils,  and  careful  regulation  of  the  diet  under  super- 
vision of  some  of  the  most  noted  physicians  in  America.  But 
improvement  was  immediate  and  almost  spectacular  under  use 
of  the  Proteals,  fifteen  minims  of  Proteal  No.  45  (alfalfa  seed, 
alfalfa  meal,  and  millet  seed)  being  given  as  an  initial  dose.  The 
letter  from  the  physician  above  quoted  was  written  after  treat- 
ment had  been  continued  about  two  months. 

Three  months  later  still  a  report  from  the  patient  himself 
tells  that  he  had  discontinued  using  the  Proteals  for  about 
four  weeks  to  see  what  the  effect  would  be,  and  "although  there 
was  no  distinct  setback  I  notice  that  the  swelling  began  to  re- 
turn gradually  in  my  hand,  and  that  my  feet  became  more  ten- 
der." Treatment  was  therefore  resumed,  with  maximum  dosage 
of  about  twenty  minims,  and  the  next  report  received  (and  the 
last  one  to  date)  states  that  the  patient  is  "improving  steadily." 

In  this  case  the  results  were  so  spectacular  that  they  were 
known  to  every  one  in  the  community,  and  a  considerable  group 
of  rheumatoid  cases  have  been  led  to  take  the  Proteal  treatment. 
There  are  similar  groups  in  various  other  communities,  developed 
in  the  same  way,  but  I  shall  not  go  into  details  regarding  these 
or  other  cases.  Full  reports  and  an  attempt  at  the  statistical 
summary  will  be  given  in  a  book  to  be  issued  a  little  later 
under  title,  probably,  of  Proteal  Therapy  in  Theory  and  Prac- 
tice. Here  I  am  concerned  rather  with  the  general  interpreta- 
tion, and  the  fundamental  principles  of  the  protein  response. 
For  the  present  purpose  it  suffices  to  have  shown  that  in  a 
certain  number  of  cases  administration  of  the  Proteals  has  been 
followed  by  modifications  of  the  rheumatoid  condition  of  such 
character  and  under  such  circumstances  as  to  leave  it  scarcely 
open  to  doubt  that  the  administration  of  the  protein  had  a  causal 
relation  to  the  observed  favorable  sequence  of  events. 

PROTEAL  THERAPY  AND  ASTHMA  AND  PSORIASIS 
Before  attempting  a  specific  interpretation  of  the  action  of  the 
Proteals  in  rheumatoid  cases,  in  terms  of  the  Proteomorphic 
Theory,  I  would  refer  to  two  other  types  of  manifestation  of 
disturbed  protein  metabolism,  totally  different  in  their  localiza- 
tion, yet,  in  my  opinion,  having  a  certain  setiological  relationship. 
I  refer  to  bronchial  asthma  and  psoriasis. 

Both  of  these  obstinate  conditions  have  been  treated,  in  a 
small  but  striking  group  of  cases,  with  Proteals  from  my  labora- 
tory by  associated  physicians. 

Our  practical  experience  in  the  treatment  of  asthma  with  the 


184      THE   PROTEOMORPHIC  THEORY  AND  THE    NEW    MEDICINE 

Proteals  is  exceedingly  limited.  Early  in  the  year  1916  I  received 
a  letter  from  a  physician  who  said  that  another  California  physi- 
cian, a  friend  of  his,  having  read  an  article  of  mine  with  ref- 
erence to  Non-specific  Therapy  had  prepared  and  used  the  pro- 
teins of  white  of  egg  in  treatment  of  his  wife,  who  had  asthma, 
with  seemingly  curative  effect.  I  stated  this  fact  to  various 
physicians  in  the  course  of  my  lecture  tour  in  the  West  during 
the  summer  of  1917,  adding  that  there  are  some  theoretical  grounds 
for  supposing  that  the  use  of  the  Proteals  might  be  advan- 
tageous ;  notably,  the  fact  that  some  physicians  associate  the 
asthmatic  tendency  with  the  rheumatoid  condition,  and  that  there 
is  a  certain  amount  of  evidence  associating  asthma  with  protein 
infections,  as  in  those  cases  that  are  susceptible  to  horse  serum. 
The  fact  that  the  blood  in  many  cases  of  asthma  shows  a 
pronounced  increase  of  eosinophiles,  if  interpreted  in  the  light 
of  my  own  theories  as  the  functions  of  this  type  of  leucocyte, 
is  corroborative  of  the  idea  of  protein  infection;  the  invasion 
being,  according  to  my  interpretation,  conspicuously  an  invasion 
of  unbroken  protein  molecules.  Further  suggestions  along  the 
same  line  are  to  be  found  in  the  obvious  fact  that  bronchial 
asthma  is  itself  allied  to  the  spasm  characteristic  of  acute  ana- 
phylactic  shock  from  the  introduction  of  a  foreign  protein  into 
a  vein,  detailed  reference  to  which  was  made  in  an  earlier  chap- 
ter of  the  present  work. 

Partly  at  least  in  response  to  my  suggestions,  a  number  of 
physicians  have  administered  the  Proteals  to  patients  suffering 
from  asthma,  and  the  few  reports  that  have  come  from  them 
have  been  of  the  most  encouraging  and  gratifying  character. 
My  brother,  Dr.  E.  H.  Williams,  of  Los  Angeles,  California, 
who  has  had  very  wide  experience  in  the  use  of  the  Proteals 
in  various  affections,  reports  two  cases  of  asthma  that  have 
yielded  to  the  treatment  and  have  reached  a  stage  of  seeming 
cure.  The  most  spectacular  case  hitherto  reported,  however,  is 
that  of  a  patient  in  a  city  of  the  Northwest  (Oregon),  a  dentist, 
who  was  subject  to  attacks  of  such  severity  that  he  had  been 
obliged  to  discontinue  practice  of  his  profession. 

Treatment  consisted  of  the  administration  on  alternate  days 
of  five  minims  of  Proteal  No.  45,  containing  in  equal  parts  the 
proteins  of  alfalfa  seed,  alfalfa  meal,  and  millet  seed. 

In  reporting  this  case,  the  physician,  who  had  had  consider- 
able prior  experience  with  the  Proteals  from  my  laboratory  and 
with  whom  I  had  seen  a  case  of  rheumatoid  arthritis  in  consul- 
tation a  few  months  earlier,  wrote  as  follows,  under  date  of 
November  8,  1917: 

"I  have  a  very  severe  case  of  bronchial  asthma  to  which  I  have 
administered  two  doses  of  No.  45  with  immediate  and  pro- 


THE   SCIENCE   AND  ART  OF   PROTEAL  THERAPY  185 

nounced  relief.  I  wish  to  give  him  a  regular  course  of  the 
treatment." 

Under  date  of  December  22,  1917,  he  sent  a  personal  letter 
containing  this  interesting  item :  "I  want  to  tell  you  about  the 
case  of  asthma.  I  used  five  minim  doses  of  Proteal  No.  45 
every  other  day  with  the  most  striking  results.  Patient  only 
experiences  one  or  two  slight  attacks  toward  morning  which  soon 
pass  off  and  he  is  free  all  day.  Prior  to  the  Proteal  he  was  un- 
able to  do  his  practice  (he  is  a  dentist).  At  times  I  have  gone 
into  his  office  to  find  him  stretched  out  fighting  for  breath.  To 
show  you  how  well  he  is  feeling — he  went  duck  shooting  the 
other  day  and  carried  a  sack  of  grain  across  the  field  to  feed 
the  ducks,  with  no  effect  whatsoever  on  his  asthma." 

And  under  date  of  January  17,  1918,  there  is  this  letter:  "I 
wish  to  report  further  on  the  case  of  bronchial  asthma  that  I  have 
been  treating  with  your  Proteal.  My  results  are  most  remark- 
able in  that  the  case  has  resisted  every  other  line  of  treatment 
for  years.  The  patient  had  not  had  a  whole  night's  sleep  for 
three  years  to  my  personal  knowledge.  He  reports  to-day  that 
he  has  been  sleeping  soundly  for  the  last  three  weeks,  and  that 
he  had  no  trouble  whatsoever;  gaining  in  weight;  works  at  his 
profession  every  day,  all  day. 

"I  inject  five  minims  of  Proteal  No.  45  every  third  day.  I 
have  not  changed  the  type  of  protein." 

Just  a  month  later,  February  17,  the  final  report  up  to  date 
states  that  the  patient  "is  now  using  eight  minims  to  a  dose  every 
third  day,  and  is  absolutely  free  from  all  symptoms  of  asthma 
while  taking  the  Proteal  that  way." 

I  may  add  that  the  same  letters  that  tell  of  the  progress  of 
this  case  also  report  on  several  cases  of  rheumatoid  arthritis 
which  "have  all  improved  greatly,  although  the  improvement  has 
been  much  slower  than  in  the  asthma.  I  have  used  the  same 
Proteal  and  the  same  dosage  as  in  the  asthma."  Also  there  is 
report  of  a  second  case  of  asthma  which  is  "steadily  improving 
under  the  Proteal  treatment.  The  asthmatic  attacks  are  much 
less  frequent,  and  on  the  whole  she  is  getting  better  every  day." 
This  second  asthmatic  patient  is  the  wife  of  a  physician.  Pro- 
teal  No.  45  has  been  used  in  the  treatment  of  this  case  as  in  the 
other. 

I  will  here  supplement  this  report  in  specific  cases  only  by 
noting  that  the  Proteals  are  now  being  tested  on  a  series  of 
asthma  cases  in  a  large  city  hospital  by  an  associated  physician 
who  reports  tentative  results  that  are  "really  encouraging  in 
practically  every  case."  Ultimate  conclusions  from  this  elab- 
orate test  will  not  be  reached  for  some  time  to  come. 

As  to  the  treatment  of  psoriasis  with  the  Proteals.     It  should 


186      TILE   PROTEOMORPHIC   THEORY   AND   THE    NEW    MEDICINE 

be  noted  that  this  is  an  application  of  non-specific  protein  therapy 
in  which  independent  workers  have  priority.  During  the  sum- 
mer of  1917,  however,  a  co-operating  physician  using  Proteals 
from  my  laboratory  treated  several  cases  of  psoriasis  of  long 
standing  with  striking  success  in  every  case.  These  were  cases 
that  had  proved  entirely  resistant  to  antecedent  treatment  in  the 
hands  of  leading  Metropolitan  skin  specialists.  The  Proteals 
were  administered  in  relatively  small  doses  ranging  from  five  to 
ten  minims.  To  make  the  test  definitive,  there  was  no  change 
in  the  diet  of  the  patient,  and  no  local  application  whatever  was 
used.  It  was  reported  that  in  one  case  there  was  favorable 
change  in  the  eruption  in  the  course  of  ten  days,  but  that  the 
others  showed  no  marked  change  for  about  five  or  six  weeks; 
after  which  there  were  rather  rapid  and  progressive  modifica- 
tions of  favorable  character,  leading  ultimately  to  complete  dis- 
appearance of  the  eruption.  Only  one  of  the  cases  was  seen 
by  me  personally,  but  this  was  a  case  in  which  the  malady  had 
been  present  for  about  eighteen  years.  The  eruption  had  ex- 
tended over  the  entire  back  of  the  patient  at  the  time  when  the 
treatment  was  begun;  and  when  I  saw  the  patient  about  three 
months  later  the  skin  was  perfectly  smooth  and  free  from  any 
kind  of  eruption. 

It  is  a  familiar  axiom  of  medicine  that  one  case  may  prove 
nothing  at  all,  and  that  a  considerable  series  of  cases  may  prove 
quite  inconclusive  or  misleading  when  checked  by  more  compre- 
hensive experience.  But  when  the  cases  under  consideration  involve 
maladies  of  such  intractability  as  rheumatoid  arthritis,  asthma, 
and  psoriasis,  it  would  appear  that  such  results  as  those  above 
noted  are  at  least  thought-provocative.  Certainly  we  are  war- 
ranted in  making  further  tests  along  similar  lines ;  and  I  am 
glad  to  be  able  to  report  that  tests  are  being  made  on  a  com- 
prehensive scale  that  may  be  expected  presently  to  justify  more 
definite  conclusions. 

How  THEORY  EXPLAINS  PRACTICE 

Meantime  a  few  words  as  to  the  theoretical  ground  on  which 
an  explanation  of  the  possible  utility  of  the  Proteals  in  these 
conditions  of  disturbed  metabolism  may  be  based.  The  explana- 
tion will  readily  suggest  itself  to  any  one  who  has  read  the 
earlier  chapters  of  this  book  attentively.  In  particular,  it  should 
be  recalled  that  the  therapeutic  response  to  the  administration 
of  Proteals  involves  increase  in  numbers  and  (so  it  is  be- 
lieved) enhancement  of  the  enzymic  activities  of  the  red  blood 
corpuscles.  This  implies,  further,  according  to  the  Proteo- 
morphic  theory,  increased  capacity  of  the  organism  to  deal  with 


THE   SCIENCE  AND  ART  OF  PROTEAL  THERAPY  187 

the  end  products  of  protein  metabolism,  and  in  particular  with 
the  purin  bodies,  hypozanthin,  zanthin,  and  uric  acid. 

Notwithstanding  the  fluctuations  of  medical  opinion  on  the 
subject,  I  believe  that  the  uric  acid  hypothesis  is  still  the  most 
tenable  thesis  as  to  the  underlying  causation  of  the  rheumatoid 
condition  that  has  been  put  forward.  But  whatever  the  view  as 
to  this  theory,  there  is  practical  unity  of  belief  that  the  condi- 
tions under  discussion  are  associated  with  disturbances  of  protein 
metabolism.  Whether  or  not  the  purin  bases  are  chiefly  at  fault, 
there  is  failure  of  complete  and  normal  metabolism  and  elim- 
ination of  the  protein  intake.  The  administration  of  the  Pro- 
teals  tends  to  normalize  these  processes.  Very  commonly  the 
blood  in  these  cases  shows  marked  quantitative  and  qualitative 
abnormalities  of  the  corpuscles.  The  Proteals  tend  to  correct 
these  abnormalities.  Rarely  indeed  does  the  patient  fail  to  im- 
prove in  blood  conditions  and  correspondingly  in  general  clin- 
ical condition. 

Through  such  modifica  ions,  in  my  belief,  the  therapeutic  ben- 
efits of  the  Proteals  are  to  be  expected.  I  have  never  for  a 
moment  entertained  the  thought  that  the  Proteals  are  specifics 
for  the  rheumatoid  conditions.  Indeed,  I  scarcely  know  what 
the  word  specific  may  mean  in  medicine  except  as  applied  to 
an  agent  directed  against  a  particular  type  of  microrganism.  If 
any  other  use  of  the  word  be  permissible,  it  might  perhaps  be 
justifiable  to  speak  of  the  Proteals  as  specifics  for  the  condi- 
tion of  anaemia,  so  direct  and  significant  is  the  response  of  the 
blood-forming  organs  to  their  stimulus.  But  anaemia  itself  is, 
after  all,  a  condition  or  symptom  rather  than  a  disease;  and  no 
wise  physician  would  depend  upon  mere  medication  in  treating 
anaemia,  without  giving  thoughtful  attention  to  its  underlying 
causes,  and  endeavoring  to  remove  these  or  modify  them  by 
eliminating  sources  of  infection,  counseling  proper  diet,  and 
securing  the  co-operation  of  proper  hygienic  measures  in  general. 

If  this  is  true  of  the  simplest  anaemia,  it  is  assuredly  doubly 
true  of  the  complicated  anaemias  that  are  associated  with  the 
various  maladies  of  disturbed  metabolism  that  are  under  consid- 
eration in  this  book.  Above  all,  this  is  true  about  rheumatoid 
arthritis.  This  is  a  malady  that  makes  its  encroachments  with 
almost  diabolical  persistency.  It  harks  back  always,  I  believe, 
to  defective  enzymic  activities  of  the  intestinal  tract.  As  a  rule, 
it  is  associated  with  life-long  tendency  to  constipation.  Its  ex- 
istence implies  hereditary  vulnerability  of  the  joints,  combined 
with  inherited  or  acquired  deficiency  of  action  of  the  organs  of 
digestion  and  assimilation,  probably  always  associated  with 
what  for  the  patient  in  question  are  improprieties  of  diet.  There 
is  usually  the  history  of  the  habitual  ingestion  of  animal  pro- 


188      THE  PROTEOMORPHIC  THEORY  AND  THE   NEW   MEDICINE 

teins  in  excess.  The  use  of  coffee,  tea,  and  cocoa  may  often  be 
credited  with  an  active  share  in  fostering  the  condition. 

One  of  my  patients,  now  under  Proteal  treatment,  affirmed 
that  she  had  been  exceedingly  moderate  in  the  use  of  ani- 
mal foods  and  of  tea  and  coffee ;  but  presently  mentioned  that 
she  habitually  ate  from  a  quarter  to  half  a  pound  of  chocolate 
each  day  and  had  been  accustomed  to  do  so  for  many  years.  It 
is  probable  that  this  quantity  of  chocolate  would  in  itself  supply 
purin  bases  enough  to  overwork  a  set  of  red  corpuscles  other- 
wise adequate.  If  this  thesis  is  correct,  it  is  obvious  that  to 
hope  to  benefit  the  patient  greatly  by  Proteal  or  any  other  treat- 
ment without  interdicting  the  use  of  chocolate  would  be  like 
throwing  water  on  a  fire  with  one  hand  and  kerosene  with  the 
other. 

In  leaving  this  aspect  of  the  subject,  however,  I  would  again 
call  attention  to  the  fact  that  a  very  considerable  number  of 
cases  are  now  on  record  in  my  office  files  in  which  patients 
suffering  from  rheumatoid  conditions  (and  a  smaller  number  of 
cases  suffering  from  asthma  and  psoriasis)  had  proved  resistant 
to  every  dietetic,  hygienic,  and  medicinal  procedure  hitherto 
available,  and  yet  have  seemed  to  respond  to  the  Proteal  treat- 
ment so  directly  and  so  explicitly  as  to  forbid  the  supposition 
that  the  observed  improvement  was  only  a  coincidence.  Coup- 
ling these  observations  with  the  theoretical  considerations  just 
presented,  we  are  justified,  I  believe,  in  awaiting  with  a  con- 
siderable measure  of  confidence  the  results  of  a  more  elaborate 
investigation  as  to  the  use  of  the  Proteals  in  the  treatment  of 
rheumatoid  conditions,  asthma,  and  psoriasis. 

PROTEAL  THERAPY  AND  TUBERCULOSIS 

Another  important  malady  that  has  been  brought  within  the 
scope  of  Proteal  therapy  is  pulmonary  tuberculosis. 

The  first  case  of  tuberculosis  treated  was  of  a  character  to 
subject  the  method  to  the  severest  possible  test.  The  patient, 
a  man  about  35  years  of  age,  had  come  back  from  southern 
California  in  a  seemingly  hopeless  condition.  Not  only  were 
lungs  involved  in  the  most  critical  manner,  but  the  tubercular 
infection  had  spread  to  the  larynx  and  had  also  involved  two 
lumbar  vertebrae.  The  case  was  so  obvious  that  the  diagnosis 
could  have  been  made  by  any  tyro,  but  in  point  of  fact 
the  advice  of  leading  specialists  had  been  sought. 

The  specialists  had  agreed  in  pronouncing  an  absolutely  unfa- 
vorable prognosis.  Nevertheless  the  patient  showed  a  certain 
amount  of  response  to  tuberculin  treatment.  Recognizing  the 
limitations  of  this  method,  however,  as  gauged  by  fairly  wide 


THE   SCIENCE   AND  ART   OF   PROTEAL   THERAPY  189 

previous  experience,  it  was  decided,  as  a  last  resort,  to  test 
the  proteal  treatment,  which  hitherto  had  been  applied  only  to 
cancer  and  two  cases  of  rheumatoid  arthritis ;  this  decision  being 
actuated  by  the  observed  effects  of  the  remedy  in  regenerating 
the  red  corpuscles,  on  the  seemingly  plausible  assumption  that  a 
remedy  proved  to  have  extraordinary  powers  to  whip  up  the 
blood-forming  organs  must  be  of  value  in  combating  an  anaemia 
of  tubercular  origin  no  less  than  the  anaemias  of  cancer  and 
rheumatism. 

Accordingly  the  patient  was  placed  under  proteal  treatment, 
early  in  September,  1915.  The  original  Proteal  extract  was 
administered  in  the  usual  way,  hypodermically  into  the  arm,  in 
doses  of  from  10  to  20  minims,  given  on  alternate  days. 

The  result  was  nothing  less  than  spectacular.  After  the  treat- 
ment was  fairly  under  way  the  patient  declared  himself  to  feel 
a  sense  of  exhilaration  as  if  from  taking  champagne.  He  gained 
in  weight,  lost  his  cachetic  appearance ;  cough  and  expectoration 
subsided.  The  bacilli  disappeared  altogether  from  his  sputum, 
and  physical  examination  of  the  chest  gave  evidence  of  the 
development  of  reparative  processes.  After  treatment  had  con- 
tinued for  about  three  months  improvement  all  along  the  line 
was  so  great  that  the  most  searching  examination  failed  to 
reveal  any  evidence  of  active  tubercular  involvement. 

On  the  15th  of  December,  1915,  an  examination  of  the  blood 
showed  90  per  cent,  haemoglobin ;  5,600,000  red  corpuscles,  and 
8,400  white  corpuscles,  with  45.5  per  cent,  polynuclears,  35  per 
cent,  large  monocytes,  10  per  cent,  small  lymphocytes,  4  per 
cent,  eosinophiles,  and  0.5  per  cent,  basophiles. 

The  patient's  subsequent  history  was  uneventful.  The  Proteal 
treatment  was  continued  for  a  time,  at  lengthened  intervals,  and 
then  there  seemed  no  necessity  for  further  treatment.  The 
patient  had  gone  to  live  in  the  country,  and  in  the  ensuing 
summer  he  was  able  to  take  part  in  rather  active  phases  of  farm 
work.  He  has  a  somewhat  weak  back,  as  a  matter  of  course, 
from  the  former  involvement  of  the  vertebrae,  but  his  general 
health  and  condition  are  highly  satisfactory.  On  March  18,  1917, 
more  than  a  year  after  discontinuance  of  the  proteal  treatment, 
the  blood  count  showed  5,884,000  red  corpuscles  of  normal  type, 
and  9,400  white  corpuscles.  Obviously,  there  is  scant  suggestion 
in  such  a  supernormal  count  of  the  tubercular  condition,  which 
had  seemed  to  doom  the  patient  until  the  proteal  treatment  was 
instituted.  The  patient's  appearance  and  general  condition  ac- 
cord well  with  the  remarkable  blood  count. 

Another  gratifying  case  of  pulmonary  tuberculosis  is  that  of 
a  young  girl  of  22,  whose  progress  has  been  so  spectacular  as 
to  merit  especial  record. 


190     THE   PROTEOMORPHIC  THEORY  AND  THE   NEW   MEDICINE 

The  diagnosis  in  this  case,  as  in  the  other,  was  absolutely 
unequivocal.  The  physical  symptoms  were  typical :  violent  cough 
with  profuse  expectoration;  temperature  of  101,  and  pulse  of 
115;  marked  emaciation,  and  evident,  even  if  not  profound, 
cachexia.  The  rales  were  so  conspicuous  that  they  could  be  heard 
without  the  stethoscope  and  with  the  ear  at  a  distance  from 
the  chest.  Bacteriological  examination  of  the  sputum  had  been 
made,  with  positive  findings,  by  the  New  York  Board  of  Health. 
The  patient's  constitution  was  so  undermined  that  her  physician 
had  told  her  she  had  but  one  chance  in  a  thousand  to  live,  and 
that  chance  contingent  on  immediate  removal  to  the  mountains. 

Blood  examination  before  treatment  showed  3,954,000  red 
corpuscles,  but  90  per  cent,  of  these  were  misshapen  or  of  the 
conformation  that  I  am  accustomed  to  speak  as  the  sea  urchin 
type.  The  bulk  of  the  red  cells  was  not  at  all  commensurate 
with  their  number,  since  so  high  a  percentage  were  misshapen. 
The  white  cells  number  9,200,  of  which  78.5  per  cent,  were 
polynuclears,  11.5  per  cent,  small  lymphocytes,  and  9.5  per  cent, 
large  mononuclears,  and  0.5  eosinophiles. 

X-ray  examination  of  the  chest  was  made  before  treatment  by 
a  prominent  roentgenologist,  who  reported  as  follows : 

"There  are  numerous  calcified  glands  in  the  lung  lobes.  In 
the  right  lung  there  are  several  calcified  tubercles  scattered 
from  the  base  to  the  apex.  Upper  lobe  is  infiltrated,  the  infil- 
tration being  most  marked  around  the  proximal  portion  of  the 
bronchial  branches  of  the  upper  lobe.  On  deep  inspiration 
there  is  tendency  to  fixation  of  the  left  diaphragm.  The  left 
auricle  is  moderately  enlarged,  and  the  right  auricle  and  ventricle 
are  moderately  enlarged.  Diagnosis,  tuberculosis  of  the  left 
upper  lobe." 

The  administration  of  Proteal  No.  45  (alfalfa  seed,  alfalfa 
meal,  and  millet  seed  proteins)  was  carried  out  in  the  usual 
way,  beginning  with  3  minim  doses  and  increasing  to  10  minims, 
administered  hypodermically  on  alternate  days.  Changes  in  the 
patient's  condition  were  immediate,  striking,  and  highly  grati- 
fying. On  the  eleventh  day  of  treatment  it  was  recorded  that 
temperature  and  pulse  were  normal ;  that  the  cough  had  almost 
disappeared,  so  that  a  sample  of  her  sputum  was  obtained  with 
difficulty;  and  that  the  patient's  condition  of  general  health  had 
been  so  modified  that  she  expressed  a  wish  to  return  to  her 
work.  She  had  gained  two  pounds  weight. 

The  blood  count  now  showed  90  per  cent,  haemoglobin,  and 
4,500,000  red  corpuscles,  not  more  than  10  per  cent,  of  which 
were  of  the  small,  battered,  misshapen  type  which  made  up 
the  chief  complement  of  cells  before  treatment.  There  were 
occasional  normoblasts,  and  some  groups  of  platelets.  The  white 


THE   SCIENCE  AND  ART  OF  PROTEAL  THERAPY  191 

cells  numbered  9,000,  with  77.2  polynuclears,  9  per  cent,  small 
lymphocytes,  and  12  per  cent,  large  mononuclears,  1.2  eosino 
philes,  and  0.25  per  cent,  basophiles.  Thus  it  will  be  seen  that 
the  red  cells  had  increased  by  I2y2  per  cent.,  the  large  poly- 
nuclears by  25  per  cent.,  and  the  eosinophiles  by  300  per  cent. 
The  activity  of  the  blood-forming  organs  was  further  evidenced 
by  the  presence  of  a  few  lymphoidocytes  and  plasma  cells.  The 
white  cells  still  showed  some  defect  of  staining  quality,  and  a 
tendency  to  clump  at  the  end  of  the  smear ;  but,  in  general,  the 
modification  of  the  blood  fn  so  short  a  period  was  notable. 

On  the  fourteenth  day  of  treatment  a  second  X-ray  examina- 
tion was  made  and  the  report  was  as  follows: 

"There  is  no  evidence  of  an  active  process  in  the  lungs.  The 
diaphragm  is  freely  movable  and  the  area  of  increased  density 
in  the  left  upper  lobe  has  disappeared.  There  is  probably  almost 
resolution  of  the  area  which  gave  signs  of  infiltration  at  the 
examination  made  twenty  days  ago." 

Thus  it  appears  that  the  X-ray  examination  confirms  the  find- 
ings of  physical  examination,  which  had  shown  the  most  striking 
modifications  for  the  better,  and  is  consonant  with  the  observed 
modifications  of  the  blood  and  the  conspicuous  change  in  the 
patient's  appearance  and  general  health.  The  further  history  of 
this  case  was  absolutely  uneventful.  The  patient  continued  to 
improve,  and  six  months  later  she  seemed  entirely  well. 

As  there  had  been  no  change  of  residence  or  modification  of 
habits,  and  as  no  other  treatment  had  been  administered,  it  seems 
impossible  not  to  ascribe  the  changes  thus  variously  recorded 
to  the  hypodermic  injections  of  the  Proteal  solution. 

Such  observations  as  these  are  obviously  enheartening.  It  was 
natural  that  I  should  call  attention  to  these  cases  in  the  medical 
addresses  during  my  lecture  tour  of  the  summer  of  1917;  and 
it  is  perhaps  not  surprising  that  a  considerable  number  of  physi- 
cians were  moved  to  make  a  trial  of  the  Proteals  in  the  treat- 
ment of  tuberculosis.  Reports  of  a  very  encouraging  character 
have  come  from  a  considerable  number  of  these  physicians ;  and 
no  single  report  in  any  way  contraindicating  the  use  of  the 
Proteals  in  cases  of  tuberculosis. 

Meantime  my  own  personal  office  and  consultation  experience 
has  been  extended  to  a  fairly  representative  group  of  cases  of 
pulmonary  tuberculosis  at  various  stages  of  development.  It 
would  not  be  consonant  with  the  plan  of  the  present  work  to 
cite  these  cases  in  detail.  A  case  that  is  fairly  typical  in  its 
history  and  its  response  to  treatment  is  that  of  patient  Number 
2,089,  with  pulmonary  tuberculosis  of  fibroid  type  of  ten  years' 
standing.  Usual  history  of  forced  feeding,  temporary  change 
of  climate,  and  more  or  less  steady  progress  in  the  wrong  direc- 


192      THE   PROTEOMORPHIC  THEORY  AND  THE   NEW   MEDICINE 

tion.  Two  hemorrhages  in  the  past  two  years.  Temperature 
never  very  high;  seldom  much  above  one  hundred.  Pulse  88  to 
100.  Haemoglobin  70;  red  corpuscles  4,088,000,  varying  in  size, 
with  many  microcytes ;  white  corpuscles  14,000. 

Treatment  began  with  three  minims  of  alfalfa  seed  protein 
(Proteal  No.  39) ;  continued  on  alternate  days,  increasing  minim 
by  minim  until  a  dosage  of  ten  minims  was  reached.  A  shift 
was  then  made  for  a  few  successive  treatments  to  Proteal  No. 
60  (alfalfa  seed  and  alfalfa  meal  proteins),  one  dose  of  which 
produced  a  rather  severe  local  reaction,  which  did  not  recur 
with  subsequent  doses.  After  about  three  weeks  of  treatment 
a  further  shift  was  made  to  Proteal  No.  45  (alfalfa  seed,  alfalfa 
meal,  and  millet  seed  proteins),  beginning  with  five  minims,  and 
gradually  increasing  the  dose  to  nine  minims. 

Throughout  this  period  of  treatment  there  was  steadily  pro- 
gressive clinical  betterment;  a  tendency  of  the  temperature  to 
approximate  the  normal  (falling  once  to  97.4)  ;  and  of  the  pulse 
to  decrease  from  98  and  100  of  the  earlier  visits  to  84,  80,  and, 
in  the  course  of  six  weeks,  a  fairly  constant  level  of  72.  Cough 
decreased,  and  character  of  sputum  changed  from  thick  and  puru- 
lent to  thin  and  whitish.  The  patient's  color,  appetite,  and  sense 
of  well-being  were  conspicuously  changed  in  a  favorable  direction. 

Meantime  there  had  been  marked  reduction  in  the  quantity  of 
albumen  in  the  urine,  which  had  been  a  complicating  factor,  and 
the  blood  count  had  shown  a  steady  progression.  On  the  twen- 
tieth day  the  red  corpuscles,  numbering  4,328,000,  and  the  white 
corpuscles  held  at  14,000.  On  the  tweny-eighth  day  the  red 
corpuscles  numbered  4,704,000,  and  the  white  corpuscles  13,600. 
On  the  forty-third  day  the  red  corpuscles  numbered  only  4,304,- 
000,  but  were  large,  round,  normal-looking  for  the  most  part, 
very  few  of  them  tending  to  take  the  purple  stain,  as  many  of 
them  had  on  a  previous  examination ;  and  the  white  corpuscles 
had  dropped  to  8,000.  On  the  sixtieth  day  the  red  corpuscles 
numbered  5,168,000,  one-third  of  them  remaining  smooth  and 
normal-looking  after  two  hours  in  the  counting  chamber,  and 
another  third  of  large  size,  though  crenated.  A  fair  proportion 
of  the  red  corpuscles  remained  large  and  fairly  smooth  after 
twenty-four  hours  in  the  Toisson  fluid.  The  white  corpuscles, 
stained  for  the  most  part  of  a  fairly  pale,  opal  blue  in  this  fluid, 
numbered  only  9,000. 

Taken  in  connection  with  the  clinical  symptoms,  this  blood 
count  of  the  sixtieth  day  showed  the  corpuscles  in  virtual  com- 
mand of  the  mixed  infection.  An  earlier  examination  had  shown 
a  marked  reduction  in  the  tubercle  bacilli,  only  one  or  two  re- 
maining to  the  field.  It  now  seemed  desirable  to  minimize  the 
total  quantity  of  protein  introduced  hypodermically,  while  main- 


THE   SCIENCE   AND   ART  OF   PROTEAL  THERAPY  193 

taining  or  accentuating  the  impulse  to  the  blood-forming  organs, 
and  it  was  thought  that  this  might  be  accomplished  by  using 
small  doses  (three  or  four  minims)  of  Proteal  No.  65,  a  com- 
bination of  the  proteins  of  alfalfa  seed,  alfalfa  meal,  millet  seed, 
rape  seed,  and  mustard  seed. 

Such  is  the  standing  of  the  case  at  the  moment  of  the  pres- 
ent writing :  Temperature  and  pulse  normal ;  blood  conditions 
all  that  could  be  desired ;  cough  and  sputum  favorably  modified ; 
kidney  complications  minimized;  patient's  skin  with  healthy 
glow;  blood  pressure  110;  conspicuous  physical  and  mental 
buoyancy. 

It  is  perhaps  of  interest  to  add  that  this  patient  had  at  the 
outset  a  slight  hyperthyroid  complication,  the  right  lobe  of  the 
thyroid  gland  being  conspicuously  enlarged.  The  rapid  pulse 
and  a  certain  nervous  hypersesthesia  were  no  doubt  in  part  asso- 
ciated with  this  condition.  As  an  auxiliary  to  the  Proteal  treat- 
ment, the  patient  was  given  one  to  two  drops  of  a  saturated 
solution  of  potassium  iodide  three  times  daily  for  five  or  six 
weeks,  at  the  end  of  which  time  the  gland  had  been  reduced  to 
normal  size.  No  other  internal  medication  of  any  kind  was 
employed.  There  had  been  from  the  outset  a  modification  of 
diet,  however.  As  is  my  custom  with  all  cases  suffering  from 
protein  intoxication,  whether  or  not  of  bacterial  origin,  I  had 
placed  the  patient  largely  on  a  vegetable  and  milk  diet.  The 
building  up  of  the  red  cell  count  and  improvement  in  quality 
under  Proteal  treatment,  associated  with  the  cessation  of  forced 
feeding  with  meat  and  eggs,  is  an  observation  that  has  been  dupli- 
cated in  many  other  cases  not  only  of  tuberculosis  but  of  various 
other  asthenic  conditions,  including  cancer.  The  theoretical  ex- 
planation is  that  proteins  in  large  excess  overtax  the  red  cor- 
puscles (in  the  handling  of  the  end  products),  and  increase  the 
anaemia  they  are  supposed  to  combat.  But  on  the  other  hand  the 
protein  intake  must  not  be  cut  too  low.  The  nitrogen  balance 
must  be  maintained. 

While  repeating  that  I  make  no  attempt  here  to  present,  even 
in  summary,  the  total  experience  in  the  treatment  of  tuberculosis 
with  Proteals,  I  cannot  refrain  from  presenting  very  condensed 
histories  of  a  small  group  of  cases  under  treatment  by  an  associ- 
ated physician  in  the  State  of  Washington,  who,  as  a  result  of 
these  preliminary  observations,  now  has  under  Proteal  treatment 
a  large  group  of  cases  of  tuberculosis  of  which  records  will  ulti- 
mately be  available.  The  condensed  reports  of  the  three  cases 
to  which  the  Proteals  were  first  administered  are  as  follows : 

(1)  Mrs.  K.  B.,  56,  Pulmonary  tuberculosis.  Involvement  of 
upper  half  of  right  lung  and  upper  one  fourth  of  left  lung.  The 
Proteal  treatment  began  with  two  and  a  half  minims  of  No.  45, 


194      THE  PROTEOMORPHIC   THEORY   AND  THE    NEW    MEDICINE 

increasing  one-half  minim  every  other  day  until  seven  minims 
were  given;  then  dose  every  fifth  day,  seven  and  one-half  minims 
per  dose.  Still  on  Proteal  No.  45,  fifteen  minim  dose.  Result 
after  ninety  days:  Reduction  in  temperature  from  103-104^2  to 
99-100^.  No  more  night  sweats.  No  cough.  Increased  appe- 
tite and  weight.  Haemoglobin  increase  to  90  per  cent.,  red  cor- 
puscles to  4,200,000.  Considerable  fibrosis  of  both  lungs. 

(2)  Mrs.  H.  F.,  age  35.     Pulmonary  tuberculosis  with  pleu- 
risy, two  years'  standing,  left  side.     Involvement  of  apex  of  right 
lung  and  entire  left  pleura.     Proteal  treatment  began  with  four 
minims  No.  45,  increasing  one  minim  every  third  day  till  seven 
minims  were  given ;  then  repeating  same  dose  every  five  days  for 
three  to  four  doses  before  increasing  dosage  one  minim  again. 
Still  on  Proteal  No.  45,  fourteen  minim  doses.     Result  after 
ninety  days :    Right  apex  clear  of  rales,  moisture,  and  all  symp- 
toms of  infection.     One-half  left  pleura  clearing  up.     Reduction 
of  temperature,  gradually,  from  102-103^2  to  normal.     Increased 
appetite.     Able  to  lie  on  left  side  for  the  first  time  in  two  years. 
Blood  picture  improved  to  nearly  normal.     All  symptoms  im- 
proved. 

(3)  Mrs.  C.  D.  E.,  age  20.     Pulmonary  tuberculosis.     Both 
upper    lobes    involved.      Proteal    treatment    began    with    three 
minims  No.  45,  increasing  one  minim  every  other  day  till  eight 
minims  were  given ;  then  the  same  dose  every  third  day  for  three 
or  four  doses,  after  which  the  dose  increased  one  minim,  etc. 
Result  of  treatment  after  ninety  days:    Temperature  normal. 
Cough    decreased.      Blood    picture    same    as   before   treatment. 

Such  observations  as  these  are  certainly  stimulative.  I  have  in 
hand  a  considerable  body  of  similar  testimony  from  physicians 
in  various  parts  of  the  country,  and  fresh  evidence'  comes  to  me 
week  by  week.  The  experience  of  these  associated  physicians, 
coupled  with  my  personal  observations,  appears  to  me  to  justify 
the  hope  that  in  the  Proteals  we  have  new  weapons  to  aid  the 
physician  in  coping  with  a  malady  which,  although  measurably 
checked  in  onslaught  in  recent  years,  still  has  a  mortality  rate 
of  about  145  per  hundred  thousand  population — a  malady  of 
which,  otherwise  stated,  claims  about  145,000  victims  in  a  year  in 
the  United  States  alone  and  not  far  from  a  million  in  the  civilized 
world. 

It  will  be  understood,  of  course,  that  no  suggestion  is  made 
that  the  Proteals  exercise  a  specific  function  in  combating  the 
tubercular  condition.  Their  action  here,  as  elsewhere,  is  directly 
on  the  blood-forming  organs  in  accordance  with  the  fundamental 
principles  of  antigenic  response.  But  the  secondary  effect  on 
the  intruding  protein  masses  constituting  areas  of  infection  in 
the  lungs  or  elsewhere  is  so  natural  a  consequence  that  it  might 


THE    SCIENCE   AND  ART  OF   PROTEAL  THERAPY  195 

have  been  expected,  and  was  in  point  of  fact  predicted  by  me  as 
a  probable  sequel — a  prediction  of  so  definite  and  tangible  a  char- 
acter as  to  have  led  to  the  original  clincal  tests  above  described, 
and,  sequentially,  to  the  more  comprehensive  tests  that  are  now 
under  way  in  various  sanitariums  and  hospitals  and  in  the 
hands  of  a  large  number  of  private  practitioners. 

In  an  earlier  section  of  this  book  I  have  called  specific  atten- 
tion to  the  similarity  of  the  blood  conditions  in  advanced  cases 
of  tuberculosis  and  of  cancer.  I  would  reiterate  here  the  not 
altogether  unfamiliar  doctrine  that  the  tubercular  subject  does 
not  as  a  rule  die  of  direct  poisoning  by  the  tubercle  germ,  but 
of  secondary  infection  associated  with  other  types  of  micro-or- 
ganisms, and  with  the  ultimate  development  of  degenerative 
protein-product  masses  in  the  lungs  or  elsewhere,  partial  hydrol- 
ysis and  absorption  of  which  produces  a  toxaemia  strictly  com- 
parable to  the  toxaemia  of  malignant  neoplasms. 

There  was  every  apriori  warrant,  therefore,  for  the  prediction 
that  the  blood  corpuscles  might  be  stimulated  by  protein  therapy 
to  do  something  toward  proteolizing  and  eliminating  from  the 
system  the  obnoxious  protein  masses  that  owed  their  inception, 
to  be  sure,  to  the  original  invasion  of  the  tubercle  bacillus,  but 
which  have  now  become  in  effect  malignant  neoplasms;  totally 
different,  assuredly,  from  the  masses  usually  classified  as  cancer- 
ous in  their  histological  structure  and  in  the  specific  type  of 
irritant  associated  with  their  genesis ;  yet  fundamentally  akin  to 
cancer  in  that  their  development  was  conditioned  on  relative 
failure  of  the  corpuscular  activities,  and  in  their  inherent  tend- 
ency to  engender  progressive  exhaustion  of  the  blood-forming 
mechanism  and  ultimately  to  terminate  the  life  of  the  individual 
in  whose  body  they  develop. 

The  analogy  of  the  observed  effect  of  Proteal  treatment  of 
cancer,  therefore,  gives  additional  support  to  hopeful  prognosti- 
cations as  to  the  value  of  the  Proteals  in  tuberculosis,  founded 
theoretically  on  the  Proteomorphic  theory  and  practically  on 
observation  of  a  limited  number  of  very  striking  cases  hitherto 
subjected  to  this  treatment.  By  the  time  my  projected  book  on 
Proteal  Therapy  is  ready  for  the  press,  there  is  every  prospect 
that  a  body  of  evidence  will  be  in  hand  that  will  answer  unequivo- 
cally the  question  as  to  the  ultimate  value  and  the  limitations  of 
Proteal  Therapy  in  its  application  to  tuberculosis. 

Meantime,  in  order  to  round  out  this  preliminary  survey  of  the 
present  status  of  the  method,  we  may  now  turn  to  a  considera- 
tion of  the  use  of  the  Proteals  in  those  conditions  of  blood  dis- 
turbance in  which  the  aetiological  factors  are  so  obscure  that  the 
blood  conditions  themselves  have  taken  rank  as  specific  maladies 
under  the  name  of  anaemias  and  leukaemias ;  in  the  antagonizing 


196      THE   PROTEOMORPHIC   THEORY   AND  THE    NEW    MEDICINE 

of  which  conditions  the  Proteals  exercise  so  direct  a  function 
that  here,  if  anywhere,  their  action  might  be  said  to  be  specific. 
In  makng  this  survey,  however,  I  shall  constantly  have  in  mind 
the  thesis  that  the  anaemias  and  leukaemias  are,  in  the  last  analy- 
sis, secondary  conditions ;  the  so-called  primary  anaemias  being, 
in  my  belief,  usually  associated  with  conditions  of  intestinal 
toxaemia,  and  being  therefore  inseparably  linked  with  the  other 
conditions  of  disturbed  protein  metabolism  that  have  all  along 
engaged  our  attention.  The  word  anaemia  is  after  all  only  a 
convenient  name  for  a  condition  that  is  a  necessary  precursor  or 
concomitant  of  all  types  of  chronic  toxaemia.  For  the  moment, 
however,  we  are  to  focus  attention  on  the  blood  conditions  them- 
selves, and  to  view  from  a  slightly  new  angle  the  effect  of  the 
Proteals  in  dealing  with  these  disturbed  conditions. 

INTESTINAL  TOXEMIA  AND  THE  ANEMIAS  AND  LEUKAEMIAS 
UNDER  PROTEAL  TREATMENT 

In  the  Monograph  of  December  1,  1916,  I  gave  a  brief  prelim- 
inary account  of  an  interesting  case,  in  which  there  was  chronic 
protein  (intestinal)  toxaemia  in  which  the  red  cells  had  the  quali- 
tative features  of  pernicious  anaemia,  although  not  reduced  in 
numbers  as  in  full  development  of  that  malady ;  and  in  which 
there  was  pronounced  leucocytosis,  with  embryonic  (ontogenetic) 
types  of  cells  suggesting  a  leukaemic  tendency. 

A  typical  count  before  treatment  showed  3,850,000  red  cells 
(crenated,  vacuolated ;  anocytosis ;  poikilocytosis,  pronounced 
chromophilia ;  normoblasts,  megalocytes) ;  very  few  platelets; 
and  57,000  leucocytes,  with  70.6  per  cent,  polynuclears  (full  cyto- 
plasm, feebly  granular,  non-acidophile) ;  21.6  lymphocytes 
(mostly  small  and  very  basophile)  ;  5.4  per  cent,  large  mononu- 
clears  (one-third  lymphoidocytes)  ;  2.6  per  cent,  eosinophiles. 

After  six  days  of  Proteal  treatment  (four  doses  of  4  to  8 
minims,  hypodermically  into  arm),  red  cells  advanced  to  5,012,000 
in  number  and  much  less  abnormal  in  appearance;  normoblasts 
exceedingly  rare,  some  groups  of  platelets ;  number  of  white 
cells  reduced  to  5,100,  with  51  per  cent,  polynuclears,  30.5  per 
cent,  small  lymphocytes,  14  per  cent,  large  mononuclears,  2.5  per 
cent,  eosinophiles,  and  2  per  cent,  basophiles.  Patient's  general 
condition  and  subjective  symptoms  very  markedly  changed  for 
the  better,  as  might  be  expected. 

This  case  appears  so  remarkable,  that  I  perhaps  cannot  do 
better  than  to  use  the  record  of  its  blood  modification  as  a  text 
to  guide  the  brief  but  explicit  study  of  this  aspect  of  the  subject. 
Of  course  it  is  not  to  be  overlooked  that  very  sudden  changes  in 
the  blood  count,  and  even  in  the  quality  of  the  cells,  may  occur 


THE   SCIENCE   AND  ART  OF   PROTEAL  THERAPY  197 

spontaneously — the  word  spontaneous  being  of  course  merely 
an  expression  of  our  ignorance — in  cases  of  pernicious  anaemia 
and  leukaemia.  But  in  the  present  instance,  the  patient  had  been 
under  observation  and  under  treatment  of  the  conventional  type 
for  a  long  period  before  Proteal  medication  was  resorted  to,  and 
we  are  justified,  I  think,  in  feeling  a  certain  measure  of  confidence 
that  the  blood  changes  noted  were  the  result  of  the  administration 
of  the  vegetable  proteins,  and  not  merely  an  accidental  concomi- 
tant of  such  administration.  In  any  event,  it  will  be  of  interest  to 
follow  the  subsequent  history  of  the  case  before  attempting  the 
promised  interpretation  of  the  observed  phenomena. 
Briefly  summarized,  the  record  is  as  follows: 
Between  the  sixth  and  eighth  day  (following  the  record  above 
given),  the  patient  was  in  the  country  and  had  no  Proteal  treat- 
ment. She  had  departed  somewhat  from  the  established  dietetic 
regimen,  among  other  things  eating  sausage.  On  the  eighth  day 
she  suffered  a  clinical  relapse.  Her  head  became  heavy,  and 
throbbing.  Her  ear  rang  intolerable.  She  had  no  appetite. 
Her  mental  condition  was  depressed  and  apprehensive.  These 
were  among  the  symptoms  that  had  characterized  her  malady  all 
along.  The  nausea  and  vomiting  that  had  also  characterized  it 
did  not  recur  on  this  occasion.  The  blood  count  now  showed 
4,384,000  red  corpuscles,  with  numerous  normoblasts  and  free 
microblasts,  and  abundant  platelets.  The  white  count  had 
advanced  to  12,800,  including  large  numbers  of  small  lympho- 
cytes of  such  diminutive  size  as  to  be  recognized  with  difficulty 
except  under  high  powers  of  the  microscope.  The  differential 
count  showed  15  per  cent,  polynuclears,  32  per  cent,  small  lym- 
phocytes, 8  per  cent,  large  monocytes,  and  2.6  eosinophiles. 
Thus  there  was  a  tendency  to  increase  in  polynuclears,  a  very 
marked  increase  of  small  lymphocytes,  and  a  reduction  in  the 
large  mononuclears.  More  than  half  of  the  large  mononuclears 
were  neutrophile  myelocytes. 

Proteal  treatment  was  at  once  reinstated,  the  particular  protein 
used  on  this  occasion  being  an  extract  of  rape  seed  (No.  42). 
On  the  eleventh  day  the  red  cell  count  showed  a  marked  falling 
off,  being  reduced  to  3,708,000.  The  general  aspect  of  the  red 
cells  was,  however,  much  more  satisfactory  than  at  the  outset. 
Meantime  the  white  cells  were  now  6,960.  The  differential 
count  was  highly  satisfactory,  showing  50.7  polynuclears,  28.5 
per  cent,  small  lymphocytes,  18.5  per  cent,  large  mononuclears, 
and  2  per  cent,  eosinophiles.  Of  the  large  mononuclears,  about 
30  per  cent,  were  typical  large  monocytes  and  30  per  cent,  large 
lymphocytes,  and  40  per  cent,  neutrophile  myelocytes.  As  hereto- 
fore, the  polynuclears  tended  to  stain  a  rather  pale  light  blue, 
but  the  tendency  to  clump  was  not  conspicuous  as  at  the  outset. 


198      THE   PROTEOMORPHIC   THEORY   AND   THE    NEW    MEDICINE 

The  patient's  physical  condition  was  much  better  than  on  the 
eighth  day,  but  not  so  good  as  on  the  sixth. 

Proteal  treatment  was  continued,  in  doses  of  5  to  10  minims, 
on  alternate  days,  and  the  clinical  progress  of  the  patient  was  so 
conspicuous  as  to  be  noticed  by  all  her  friends.  She  spoke  of 
herself  as  being  "quite  made  over."  The  distressing  giddiness 
disappeared  altogether ;  her  appetite  was  good,  and  she  had  no 
nausea  or  other  gastric  disturbance ;  she  slept  well,  felt  cheerful 
and  bouyant,  and  in  general  was  in  a  condition  that  simulated 
normal  health.  On  the  28th  day  of  the  treatment,  her  blood 
count  showed  4,074,000  red  corpuscles  of  fairly  normal  appear- 
ance (totally  different  in  aspect  from  the  original  condition), 
and  7,150  white  corpuscles,  of  which  52  per  cent,  were  polynu- 
clears,  28  per  cent,  small  lymphocytes,  18.5  per  cent,  large 
mononuclears,  and  1.5  eosinophiles.  The  polynuclears  stained 
blue,  but  their  cytoplasm  was  distinctly  acidophile.  The  mono- 
nuclears were  mostly  typical  large  monocytes,  with  only  a  few 
questionable  myelocytes.  No  normoblasts  were  seen,  but  there 
was  a  fair  number  of  platelets.  Except  that  the  red  cells  were 
not  quite  as  numerous  as  might  be  desired,  this  blood  picture  is 
in  the  highest  degree  satisfactory. 

On  the  35th  day,  the  defect  in  the  red  corpuscles  had  been 
remedied,  as  these  now  number  5,328,000.  The  quality  of  the 
red  cells  was  correspondingly  satisfactory,  being  recorded  in  the 
main  very  normal,  except  that  some  were  small.  The  white  cells 
now  numbered  7,700,  with  63.5  per  cent,  polynuclears,  13.5  per 
cent,  small  lymphocytes,  19  per  cent,  large  monocytes,  practically 
all  of  them  large  lymphocytes  or  typical  large  monocytes,  2  per 
cent,  eosinophiles,  and  only  a  negligible  number  of  myelocytes. 
It  is  recorded  that  the  polynuclears  were  of  normal  appearance 
with  cytoplasm  taking  acidophile  stain  moderately,  and  nuclei 
staining  deeply.  Large  monocytes  and  eosinophiles  were  large 
and  beautifully  typical. 

Here  it  will  be  noted  that  the  polynuclears  were  more  numer- 
ous than  in  the  preceding  counts  (although  far  short  of  their 
original  percentage),  and  that  this  increase  had  apparently  been 
made  at  the  expense  of  the  small  lymphocytes,  the  large  mononu- 
clears being  more  abundant  than  on  any  previous  occasion.  That 
this  blood  condition  was  salutary  is  evidenced  by  the  fact  that 
the  patient's  clinical  condition  continued  in  the  highest  degree 
satisfactory,  notwithstanding  that  she  had  been  for  ten  days  of 
this  period  under  excessive  mental  strain  owing  to  the  critical 
illness  of  a  member  of  her  family.  It  now  became  necessary 
for  the  patient  to  go  to  California,  and  she  accomplished  the 
journey  without  incident,  although  she  would  have  been  utterly 


THE    SCIENCE    AND   ART   OF    PROTEAL   THERAPY  199 

unable  to  undertake  such  a  voyage  six  weeks  earlier,  before  be- 
ginning the  Proteal  treatment. 

At  the  end  of  the  journey,  the  patient  was  subjected  to  both 
mental  and  physical  strain  for  a  term  of  weeks,  during  which 
time  she  had  only  occasional  doses  of  Proteals,  and  was  not  under 
observation  as  to  the  blood  count.  It  was  reported  that  she 
stood  the  strain  amazingly  at  first,  but  subsequently,  after  four 
or  five  weeks,  suffered  a  relapse,  with  recurrence  of  spells  of 
dizziness  and  a  feeling  of  general  debility.  Proteal  treatment 
was  resumed,  and  continued  with  clinical  benefits,  after  the 
patient's  return  to  New  York,  No.  45  being  chiefly  used,  in 
doses  of  five  to  eight  minims,  administered  at  lengthening  inter- 
vals, and  finally  discontinued  about  six  months  after  the  initial 
treatment. 

On  March  30,  1917,  the  blood  picture  was :  Haemoglobin,  90 ; 
red  corpuscles,  5,152,000;  leucocytes,  5,000,  with  56  per  cent, 
polynuclears,  18.5  small  lymphocytes,  24  per  cent,  large  mono- 
cytes,  and  1.5  eosinophiles.  On  May  16,  the  count  showed  4,744,- 
000  erythrocytes  and  5,600  leucocytes.  Seven  months  later  (De- 
cember 11),  with  no  treatment  since  June,  the  blood  showed 
4,912,000  red  cells  and  6,000  white;  and  on  January  28,  1918, 
fourteen  months  after  the  original  use  of  the  Proteals,  the  exam- 
ination showed  5,528,000  red  cells  and  8,600  leucocytes. 

Clinically,  the  patient  has  attained  a  condition  of  fairly  robust 
health,  all  the  disturbing  symptoms  having  disappeared ;  and 
such  is  her  condition  at  the  moment  of  present  writing,  sixteen 
months  after  the  institution  of  the  Proteal  treatment  and  eight 
months  after  it  was  discontinued. 

It  is  worth  while  to  make  inquiry  as  to  whether  a  satisfactory 
theoretical  explanation  can  be  found  of  such  striking  modifica- 
tions of  the  blood  count  as  are  above  recorded,  in  particular  with 
reference  to  the  spectacular  decrease  in  the  number  of  white 
corpuscles  at  the  outset.  It  should  be  added  that  I  have  had 
no  closely  similar  case  with  equally  marked  leukaemic  tendency 
in  which  so  spectacular  an  effect  was  observable ;  but,  on  the 
other  hand,  I  have  numerous  records,  some  of  which  have  al- 
ready been  presented,  of  cases  in  which  the  white  blood  cell  count 
has  been  very  rapidly  reduced  from  12,000,  14,000,  and  16,000  to 
the  normal  by  a  few  doses  of  vegetable  proteins.  How  shall  we 
account  for  this  striking  phenomenon? 

BLOOD  CHANGES  TENTATIVELY  EXPLAINED 

It  is  desirable  to  say  that  the  explanation  about  to  be  given 
is  put  forward  tentatively.  We  know  too  little  about  the  genesis 
and  transformations  of  the  blood  corpuscles  to  speak  dogmati- 


200      THE    PROTEOMORPHIC   THEORY    AND   THE    NEW    MEDICINE 

cally  on  this  aspect  of  the  subject.  Nevertheless,  I  think  that 
data  are  sufficient  to  enable  us  to  suggest  at  least  a  plausible  hy- 
pothesis as  to  the  modus  operandi  of  white  cell  decrease  or  modi- 
fication in  direction  of  the  normal  under  Proteal  treatment.  A 
clue  to  the  explanation  is  to  be  found,  it  seems  to  me,  in  the  com- 
plementary or  compensatory  relation  that  exists  between  the 
white  and  the  red  corpuscles.  All  theories  aside,  it  has  long 
been  known  that  when  there  is  sudden  reduction  in  the  mass  of  the 
blood,  through  hemorrhage,  a  rapid  leucocytosis  supervenes,  it 
being  apparently  a  more  facile  matter  to  increase  the  leucocyte 
population  than  to  bring  the  red  corpuscles  back  to  normal  num- 
bers. The  difference  in  bulk  between  the  two  perhaps  explains 
this  more  or  less  adequately,  it  being  recalled  that  the  red  cell 
population  is  normally  from  500  to  one  thousand  times  the  census 
of  the  white  corpuscles.  It  will  be  recalled,  also,  that  under 
normal  conditions  there  is  a  far  wider  range  of  variation  in  the 
number  of  white  corpuscles  than  in  the  red.  A  normal  post- 
prandial leucocytosis  may  increase  the  numbers  of  white  cor- 
puscles by  50  per  cent;  and,  contrariwise,  a  corresponding 
reduction  takes  place  a  few  hours  later.  No  such  oscillation 
as  this  occurs  under  normal  conditions  in  the  red  cell  population. 

If  the  post-hemorrhagic  leucocytosis  be  accepted  as  in  a  sense 
compensatory,  it  must  be  assumed  that  the  leucocytes  are  able 
to  some  extent  to  perform  the  work  of  the  red  corpuscles. 
Speaking  in  terms  of  the  Proteomorphic  theory,  we  may  assume 
that  there  is  no  absolutely  fixed  line  of  demarcation  between  the 
proteolytic  activities  of  the  white  corpuscles  and  red.  (I  shall 
present  below  the  record  of  a  case  of  leukaemia,  that  strikingly 
emphasizes  this  view.)  The  theory  assumes  that  the  red  cor- 
puscles are  incapable  of  dealing  with  the  full-sized  protein  mole- 
cule, and  that  the  white  corpuscles  cannot  adequately  care  for 
the  later  products  of  hydrolysis,  of  the  pelypeptid  order.  But  in 
all  probability  there  are  intermediate  stages  at  which  the  activ- 
ities of  the  two  sets  of  corpuscles  overlap.  It  is  conceivable, 
for  example,  that  both  the  white  corpuscles  and  the  red  may  be 
able  to  deal  more  or  less  adequately  with  molecules  at  the  peptone 
stage,  and  that  the  white  corpuscles  may  hand  the  material  over, 
so  to  speak,  to  the  red  corpuscles  at  somewhat  variant  stages  of 
decompounding  under  different  conditions. 

If  we  assume,  as  was  done  in  the  Proteomorphic  theory,  that 
the  disruption  of  the  white  corpuscle  and  the  consequent  libera- 
tion of  its  contents  takes  place  as  the  result  of  osmotic  pressure, 
and  that  this  pressure  is  due  to  the  decompounding  of  the  protein 
molecules  within  the  substance  of  the  leucocytes,  it  is  at  least 
conceivable  that  the  stage  of  decompounding  at  which  disruption 
will  occur  is  dependent  in  a  measure  on  the  quantity  of  protein 


THE   SCIENCE   AND   ART   OF   PROTEAL  THERAPY  201 

which  the  white  corpuscle  has  ingested.  It  will  be  recalled  that, 
according  to  Van't  Hoff's  theory,  each  individual  molecule,  what- 
ever its  size,  presses  with  equal  force  in  a  liquid  medium.  If, 
then,  in  a  given  case,  a  leucocyte  has  ingested  a  large  quantity 
of  protein,  the  decompounding  of  this  protein  might  produce  a 
sufficient  number  of  molecules,  at,  let  us  say,  the  proteose  stage 
to  exert  a  disruptive  force  on  the  leucocytic  membrane ;  whereas, 
had  the  amount  of  protein  originally  ingested  been  smaller, 
decompounding  to  the  peptone  stage  might  have  been  necessary 
before  an  equivalent  pressure  was  exerted. 

If  this  suggestion  be  accepted,  it  follows  that,  given  a  fixed 
quantity  of  protein  papulum  in  the  blood,  the  larger  the  number 
of  leucocytes  the  smaller  would  be  their  average  intake  of  protein, 
and  hence  the  more  complete  the  average  stage  of  decompound- 
ing before  disruption.  In  other  words,  the  larger  the  number  of 
leucocytes,  the  more  efficient  their  work  as  protein  hydrolyzers. 
Where  a  small  number  of  leucocytes  must  have  turned  over  their 
product  to  the  red  corpuscles  at  the  peptone  stage,  a  larger  num- 
ber of  leucocytes  may  reduce  it  all  to  the  polypeptid  stage,  and 
thus,  seemingly,  conserve  the  resources  of  the  red  corpuscles  by 
limiting  the  work  put  upon  them. 

If  such  are  indeed  the  relations  of  white  and  red  corpuscles, 
and  the  hypothesis  just  suggested  be  accepted  as  plausible,  a  high 
leucocyte  count  such  as  that  recorded  in  the  case  of  the  patient 
above  reported  (57,000)  must  be  accepted  as  a  salutary  attempt 
on  the  part  of  the  organism  to  compensate  for  the  inadequacy 
of  the  red  corpuscles,  indicated  not  only  by  their  small  number 
(3,850,000)  but  also  by  their  extreme  defects  of  size  and  quality. 
This  was  a  case,  seemingly,  where  chronic  intestinal  defects  of 
secretion  of  the  digestive  enzymes  (pancreatic,  biliary,  or  enteric) 
persistently  led  to  the  introduction  into  the  blood  of  protein 
products  not  hydrolyzed  to  the  normal  polypeptid  or  amino-acid 
stage.  This  put  an  incessant  strain  on  the  red  corpuscles,  which 
probably  (could  the  full  history  of  the  case  be  known)  were  for 
a  time  increased  in  number,  but  which  ultimately,  owing  to  ex- 
haustion of  the  blood-forming  mechanism  through  long  sub- 
jection to  the  same  toxin, .  became  decreased  in  number  and 
utterly  dyscrasic  in  quality. 

Then  came  the  increase  of  white  corpuscles  to  endeavor  to 
compensate  the  defects  of  the  red  cells.  The  white  cells  would 
accomplish  this,  according  to  hypothesis,  by  handling  as  effec- 
tively as  possible  the  larger  protein  molecules  normally  or 
abnormally  present  in  the  blood.  If,  however,  the  intermediate 
and  later  products  of  hydrolysis  continue  to  intrude  themselves 
in  excessive  quantities,  the  strain  on  the  blood  corpuscles  would 
be  cumulative,  and  even  though  the  white  corpuscles  were  pro- 


202      THE    PROTEOMORPHIC   THEORY    AND   THE    NEW    MEDICINE 

duced  in  larger  and  yet  larger  phalanxes,  disaster  must  in  the 
end  result,  since  no  quantity  of  white  corpuscles  could  compen- 
sate altogether  for  the  lack  of  reds,  inasmuch  as  the  red 
corpuscles  alone  are  capable  of  dealing  with  the  end-products 
of  protein  decompounding. 

The  time  would  come,  apparently,  when  the  increase  of  white 
corpuscles  passes  the  point  of  maximum  efficiency,  the  amount 
of  protein  papulum  for  each  being  so  small  that  a  relatively  long 
life  is  vouchsafed  to  each  white  corpuscle  before  its  contents 
reach  the  stage  of  disruptive  pressure.  There  would  then  be 
an  accumulation  of  old  white  corpuscles  in  the  blood,  piling  up 
ultimately  in  such  numbers  as  to  produce  the  enormous  counts 
familiar  in  advanced  stages  of  leukaemia. 

On  the  other  hand,  under  such  conditions,  the  protein  content 
of  each  individual  white  corpuscle  would,  on  the  average,  be 
reduced  to  an  exceedingly  low  stage  of  hydrolysis,  that  is  to  say, 
to  the  lowest  stage  to  which  the  leucocytic  enzymes  can  reduce 
it;  and,  on  disruption,  the  leucocytes  would  supply  the  red  cor- 
puscles with,  let  us  say,  polypeptids  (perhaps  dipeptids  or  mono- 
peptids),  making  the  smallest  possible  requirement  on  their 
enzymic  activities.  Should  something  take  place  that  would 
cause  the  disruption  even  of  the  major  part  of  the  white  cor- 
puscles in  a  brief  period,  the  amount  of  toxicity  to  the  nervous 
system  that  would  result  would  depend  entirely  on  the  equipment 
of  red  corpuscles.  Moreover,  it  is  not  impossible  that  when  the 
red  corpuscles  are  abundant,  their  enzymes  may  have  a  catalytic 
effect  on  the  white  corpuscles,  stimulating  them  to  greater 
enzymic  activity,  and  thus  facilitating  their  disruption.  That 
some  such  complementary  relation  between  the  red  corpuscles 
and  the  white  exists,  might  reasonably  be  expected,  similar 
adjustments  between  organs  of  complimentary  function  being 
familiar  throughout  the  organism.  An  agent  which  stimulated 
the  production  of  increased  members  of  red  corpuscles,  or  one 
that  increased  the  enzymic  activities  of  these  corpuscles,  would 
thus,  secondarily,  result  in  effecting  the  more  rapid  decom- 
pounding of  the  white  corpuscles,  thereby  reducing  their  number. 

I  am  disposed  to  think  that  this  line  of  reasoning  explains  the 
rapid  decrease  of  white  corpuscles  in  the  case  above  cited. 
It  will  be  recalled  that  coincidentally  with  this  decrease  in  white 
corpuscles  there  was  an  increase  of  red  corpuscles  from  3,850,000 
to  5,012,000, — an  increase,  in  other  words,  of  more  than  30  per 
cent.  The  size  and  quality  of  the  individual  corpuscle  were  more 
than  correspondingly  enhanced,  so  it  may  plausibly  be  assumed 
that  the  enzymic  capacities  and  activities  of  the  red  corpuscles 
as  a  whole  were  measurably  doubled.  The  increased  red  cell 
enzymes  stimulating  white  cell  catabolism,  and  the  red  cells  now 


THE    SCIENCE    AND   ART   OF    PROTEAL   THERAPY  203 

being  adequate  to  deal  with  the  end-products  of  protein  hydroly- 
sis thus  liberated,  the  excess  accumulation  of  white  corpuscles 
would  be  immediately  done  away  with,  and  the  mother  cells  of 
the  leucocytes,  being  no  longer  stimulated  to  excessive  activity, 
might  resume  their  normal  rate  of  functioning.  Indeed,  it  is 
consistent  with  what  has  been  suggested,  to  assume  that  in  such 
a  case  as  the  above,  where  leukaemia  had  not  been  far  developed, 
the  leucocytic  mother  cells  had  not  acted  with  extreme  prolific- 
ness,  and  that  the  large  leucocytic  population  was  due,  in  large 
measure,  to  accumulation  rather  than  to  over  production. 

On  these  assumptions,  the  only  mystery  connected  with  the 
matter  would  be  the  fact  of  the  extraordinary  regeneration  of 
the  red  cells  themselves  under  influence  of  the  Proteal  remedy. 
This  is  to  be  explained,  according  to  the  Proteomorphic  hypothe- 
sis, as  taking  place  in  connection  with  the  following  sequence  of 
events :  ( 1 )  the  vegetable  protein  introduced  hypodermically 
is  quickly  absorbed  into  the  blood  stream,  where  (2)  it  encounters 
a  multitude  of  white  corpuscles  that  quickly  ingest  it  and  effect 
its  partial  proteolysis.  Disruption  of  the  white  corpuscles  taking 
place  through  osmotic  pressure,  the  polypeptids  to  which  the 
vegetable  proteins  have  been  reduced  (circulating  now  freely  in 
the  blood)  come  in  contact  with  the  mother  cells  in  the 
marrow  with  the  effect  of  an  altogether  new  stimulus.  These 
cells,  by  hypothesis,  have  become  exhausted  to  the  stimulus  of 
the  protein  products  that  come  to  them  through  the  intestines, 
and  are  performing  their  functions  very  inadequately.  Now, 
however,  they  respond  to  the  new  impulse  with  alacrity,  and 
put  forth  a  new  generation  of  red  corpuscles  totally  different 
in  quality  from  those  that  have  been  their  recent  progeny.  These 
new  cells  are  able  to  deal  with  the  end-products  of  protein  cata- 
bolism  already  in  the  blood,  and  with  any  new  increment  that 
may  come;  and  there  is  possibility  of  a  re-establishment  of 
normal  conditions  of  metabolism. 

If,  now,  the  patient  is  placed  under  proper  dietetic  restriction, 
so  that  the  faulty  intake  of  protein  products  is  in  a  measure 
corrected;  and  if  the  Proteal  injections  are  continued  day  by  day, 
so  that  the  blood-forming  mechanism  receives  a  continuous  stimu- 
lus, conditions  are  favorable  for  a  permanent  regeneration  of  the 
blood,  and  for  the  clinical  cure  of  the  patient. 

Such,  as  I  see  it,  is  a  plausible  explanation  of  the  manner  of 
action  of  proteantigens  in  effecting  the  transformations  of  the 
blood  that  have  been  so  frequently  observed,  of  which  the  case 
above  recorded  furnishes  an  extreme  instance. 

If  this  explanation  be  accepted,  it  will  be  clear  that  the  same 
line  of  reasoning  applies  to  any  and  every  type  of  protein  intoxi- 
cation. Intestinal  toxaemia  and  cancer  are  obviously  very  differ- 


204      THE    PROTEOMORPHIC   THEORY    AND   THE    NEW    MEDICINE 

ent  conditions  (though  I  venture  to  doubt  if  the  latter  ever 
exists  without  having  been  preceded  by  the  former),  yet  the 
effects  on  the  blood  and  on  the  system  at  large  of  protein  prod- 
ucts absorbed  through  the  intestines  and  of  those  liberated  from 
cancer  tissue  may  be  substantially  identical.  (The  high  glutamic 
acid  contents  of  tumors  is  worth  recalling  in  this  connection.) 
It  is  an  observed  fact  that  many  diverse  conditions,  including 
intestinal  toxaemia,  tuberculosis,  and  cancer,  may  bring  the  blood 
to  seemingly  the  same  stage  of  abnormality,  characterized  by 
red  cells  reduced  in  number  and  of  the  pernicious  anaemia  type, 
and  by  leucocytes  increased  in  number  by  way  of  compensation, 
with  relative  neutrophilia.  It  is  not  strange,  then,  that  the  same 
line  of  treatment  may  be  applicable  to  all  these  conditions — and 
to  numerous  other  conditions  similarity  characterized  by  dis- 
turbed protein  metabolism — since  the  fundamental  maladjust- 
ments are  the  same  in  all. 

If  a  fairly  satisfactory  explanation  may  thus  be  found  of 
the  increase  of  red  corpuscles  and  the  decrease  of  leucocytes 
under  Proteal  treatment,  as  in  the  case  above  cited,  it  must  be 
admitted  that  an  explanation  of  the  striking  modification  of  the 
differential  leucocyte  count  is  not  so  readily  forthcoming. 
Nevertheless,  it  is  possible  to  offer  at  least  a  provisional  explana- 
tion, along  the  lines  of  an  hypothesis  of  differential  leucocyte 
action  presented  in  an  earlier  section.  In  examing  this  hypothe- 
sis, we  shall  have  occasion  to  consider  the  blood  modifications 
in  an  interesting  case  of  leukaemia,  already  once  or  twice  referred 
to.  For  the  moment,  however,  attention  is  directed  to  the  modi- 
fied leucocyte  count  in  the  case  of  anaemia  already  discussed. 
It  will  be  recalled  that  the  polynuclears  at  the  outset  numbered 
70.6  per  cent  of  the  total  leucocyte ;  and  that  after  a  few  days' 
treatment  their  proportion  was  reduced  to  51  per  cent.  Mean- 
time, the  small  lymphocytes  had  increased  from  21.6  per  cent,  to 
35  per  cent.,  and  the  large  mononuclears  from  5.4  per  cent,  to 
14  per  cent. 

This  would  appear  to  tell  either  of  a  disproportionate  destruc- 
tion of  mononuclears  or  of  a  no  less  disproportionate  production 
of  mononuclears.  And  the  problem  thus  presented  does  not 
apply  to  this  case  merely,  for  I  have  posited  a  similar  modification 
of  the  differential  count  as  a  characteristic  response  to  protean- 
tigen  treatment.  Reference  to  this  has  been  made  many  times 
in  the  preceding  pages ;  and  tables  demonstrating  the  modification 
in  series  of  cases  are  presented  in  the  cancer  Monograph.  What 
is  the  explanation  of  this  modification? 

Perhaps  the  simplest  explanation  of  the  change  of  polynuclears 
would  be  that  the  hydrolytic  function  of  this  type  of  leucocyte 
is  most  directly  compensatory  of  that  of  the  red  corpuscles.  It 


THE    SCIENCE   AND   ART   OF   PROTEAL   THERAPY  205 

was  suggested  above  that  the  polynuclears  deal  with  the  proteins 
at  approximately  the  peptone  stage,  carrying  hydrolysis  to  a  stage 
that  fits  the  protein  products  for  the  purposes  of  the  red  cor- 
puscles. On  this  assumption,  it  is  logical  to  suppose  that  r.s  the 
red  corpuscles  are  overworked,  neutrophile  recruits  may  be 
called  out  to  make  sure  that  the  largest  possible  proportion  of 
proteins  in  the  blood  is  reduced  to  the  polypeptid  stage,  thus  re- 
lieving, as  far  as  may  be,  the  strain  on  the  red  corpuscles. 

It  was  noted,  however,  that  the  polynuclears  unquestionably 
had  to  do  with  resistance  to  bacterial  invasion ;  and  it  was  further 
suggested  that  they  perhaps  have  to  do  with  the  decompounding 
of  fats.  These  suppositions  obviously  introduce  complications, 
which  must  be  borne  in  mind,  but  which  do  not  call  for  more 
elaborate  consideration  at  the  moment ;  inasmuch  as,  in  the  case 
under  consideration,  there  was  no  acute  bacterial  invasion  in 
question,  nor  any  sudden  modification  in  diet  on  one  hand  or  the 
patient's  weight  on  the  other  suggesting  a  change  in  the  needs 
of  the  organism  as  regards  fat  metabolism.  Yet  there  was 
apparently  a  very  sudden  modification  in  the  systemic  need  of 
polynuclear  leucocytes.  This  modification  was  associated  with 
very  marked  increase  in  the  numbers,  and  presumably  in  the 
efficiency  of  the  red  corpuscles ;  and  a  corresponding  increase  in 
numbers  and  presumptive  activities  of  the  mononuclear  cohorts. 

Viewing  the  matter  with  reference  to  these  two  essential  modi- 
fications, the  thought  obtrudes  itself  that  when  mononuclear 
leucocytes  on  one  hand  and  red  corpuscles  on  the  other  are 
working  at  maximum  efficiency,  their  joint  hydrolytic  activities 
cover  the  entire  range  of  protein  catabolism,  leaving  the  polynu- 
clears free  for  the  auxiliary  tasks  of  combating  bacteria  (with 
their  large  lipoid  content)  and  handling  fats  in  general;  possibly, 
also,  having  to  do  with  the  catabolism  of  carbohydrates, — the 
latter  possibility,  however,  being  mentioned  here  only  parenthet- 
ically, as  I  have  purposely  refrained  from  complicating  the 
problem  by  reference  to  this  group  of  alimentary  constituents. 

Elaborating  the  view  just  suggested,  we  may  assume  that  the 
large  mononuclear  leucocytes  begin  the  hydrolysis  of  proteins; 
and  that  the  small  mononuclears,  when  working  at  maximum 
efficiency,  carry  it  forward  to  the  stage  of  adequate  preparation 
for  uses  of  the  red  corpuscles,  which  ultimately  complete  the 
work  of  decompounding ;  and  that  in  proportion  as  this  simplified 
method  of  handling  is  perfected,  the  need  for  the  services-of  the 
polynuclears  in  this  connection  is  minimized. 

That  this  would  represent  to  some  extent  a  conservation  of 
bodily  energies  is  suggested  in  the  relative  complexity  of  organi- 
zation of  the  polynuclears.  Seemingly  the  mononuclears  are  cells 


206      THE   PROTEOMORPHIC   THEORY   AND  THE    NEW    MEDICINE 

of  a  more  primitive  type ;  calling  for  less  expenditure  of  energy, 
therefore,  in  their  development. 

It  will  be  obvious  that  there  is  nothing  inconsistent  in  all  this 
with  the  hypothesis  of  differential  leucocyte  functions  already  put 
forward.  The  present  view  is  merely  an  elaboration  and  exten- 
sion of  that  hypothesis.  It  has  been  urged  all  along  that  there 
is  probably  a  considerable  range  of  variation  or  latitude  as  to 
precise  proteolytic  functions  of  each  type  of  corpuscle. 

This  is  no  more  than  is  observed  everywhere  in  the  organism ; 
the  possibility  of  vicarious  functioning  being  a  necessary  safe- 
guard to  health  and  to  life  itself.  Thus  we  find  that  there  is  no 
single  organ  that  has  absolute  control  over  any  stage  or  phase 
of  food  digestion  in  the  alimentary  tract.  There  are  more  or 
less  compensatory  functions  between  salivary  glands  and  pan- 
creas, and  between  stomach,  liver,  and  the  enteric  walls.  Even 
the  highly  specialized  functions  of  the  kidney  are  in  a  measure 
duplicated  by  the  functions  of  the  glands  of  the  skin.  Moreover, 
two  kidneys  are  provided,  although  a  single  kidney  is  amply 
competent  under  ordinary  circumstances  to  meet  elimination  re- 
quirements. Similarly  there  are  two  lungs,  providing  an  aggre- 
gate alveolar  surface  vastly  in  excess  of  the  maximum  needs  of 
the  organism. 

It  is  not  strange,  then,  that  the  corpusclar  cohorts  should  show 
a  similar  margin  of  safety;  and  we  need  not  be  surprised  to  ob- 
serve that,  under  exceptional  circumstances,  metabolic  conditions 
apparently  approximating  the  normal  may  be  maintained  when 
there  has  been  a  profound  disturbance  of  the  observed  normal 
conditions  of  the  corpuscles, — just  as  a  person  with  one  kidney 
or  with  one  affected  lung  may  appear  to  retain  a  normal  level 
of  health ;  or,  to  make  a  still  closer  analogy,  as  a  patient  may  be 
maintained  for  a  considerable  period  by  rectal  feeding,  the  func- 
tions of  the  normal  digestive  glands  being  for  the  moment 
abrogated.  I  have  just  had  report  of  such  a  case  where  (owing 
to  a  gastric  ulcer)  rectal  feeding  has  been  the  sole  method  of 
alimentation  for  a  period  of  more  than  ten  months. 

A  CASE  OF  LEUKEMIA 

I  am  led  to  emphasize  this  aspect  of  the  subject  because  of 
certain  anomalies  forced  on  my  attention  by  the  case  of  lymphatic 
leukaemia  to  which  reference  was  above  made.  The  patient,  a 
man  of  65,  is  known  to  have  been  leuksemic  for  several  years. 
When  the  patient  first  came  to  me  for  examination,  he  brought 
with  him  the  report  of  a  blood  count  made  two  years  earlier 
which  showed  200,000  leucocytes.  No  blood  examination  had 
been  made  in  the  interval,  but  my  examination  revealed  upward 


THE    SCIENCE   AND  ART   OF   PROTEAL   THERAPY  207 

of  a  million  leucocytes  to  the  cubic  millimeter,  with  red  count 
not  far  above  three  million ;  the  smear  showing  the  leucocytes  to 
be  small  compact  lymphocytes  almost  exclusively. 

The  clinical  symptoms  that  led  the  patient  to  come  for  treat- 
ment consisted  chiefly  of  extreme  enlargement  of  glands  at  each 
side  of  the  neck,  in  the  region  of  the  parotids ;  enlargement  of 
lymphatic  glands  at  the  back  of  the  neck  and  head,  in  the  axil- 
lary regions  and  inguinal  regions  and  elsewhere ;  associated  with 
severe  pains,  particularly  located  in  the  region  of  the  enlarged 
glands  at  the  back  of  the  neck  and  head. 

The  patient  was  placed  under  Proteal  treatment,  the  mixture 
of  the  proteins  of  alfalfa  seed,  alfalfa  meal,  and  millet  seed  (Pro- 
teal  No.  45)  being  administered  in  doses  of  from  three  to  eight 
minims  on  alternate  days ;  a  shift  being  subsequently  made  to 
rape  seed  protein  (Proteal  No.  42).  There  was  a  very  prompt 
response,  in  that  general  reduction  in  the  size  of  the  enlarged 
glands  took  place.  The  glands  at  the  sides  of  the  neck  were 
reduced  so  markedly  as  to  alter  the  patient's  appearance  very 
noticeably.  The  lymphatic  swellings  at  the  back  of  the  neck 
and  head,  and  in  axillary  and  inguinal  regions  were  greatly  re- 
duced in  size  or  altogether  disappeared.  The  pain,  which  had 
been  persistent,  disappeared  and  has  not  recurred.  Nor  has 
there  been  any  tendency  to  return  of  the  glandular  enlargements, 
except  that  a  temporary  swelling  appeared  in  each  mastoid  region 
following  an  attack  of  influenza  (shortly  after  convalescing), 
which  swelling  the  patient  ascribed  to  "catching  cold"  through 
sitting  in  a  draft. 

I  shall  not  go  further  into  the  clinical  details  of  this  patient's 
history  in  the  present  connection.  We  are  here  concerned  with 
the  blood  conditions,  which  are  of  the  most  striking  and  (in  con- 
nection with  the  clinical  state),  even  mystifying  character.  After 
two  weeks  of  Proteal  treatment,  there  was  a  very  marked  modifi- 
cation in  the  character  of  the  leucocytes,  in  that  large  number 
of  cells  appeared  which  were  two  or  three  times  the  size  of  the 
prevalent  lymphocytes,  and  which  took  the  stain  much  more 
faintly,  and  appeared  somewhat  vague  and  ragged  in  outline  in 
contrast  with  the  sharply  rounded,  bullet-like  lymphocytes  that 
clustered  everywhere  so  thickly  as  to  remind  one  of  grapes  on 
the  vine.  These  large  cells  could  not  well  be  classified  other  than 
as  large  monocytes,  although  only  by  rare  exception  could  one 
be  found  that  showed  a  distinct  nucleus  and  dark-stained  cyto- 
plasm. In  general  these  large  cells,  like  the  small  lymphocytes, 
showed  no  cytoplasm  whatever.  They  appeared  to  be  all  nucleus, 
with  vague  boundaries.  They  gave  one  the  impression  of  lying 
in  the  background  as  it  were,  and  at  a  different  level,  from  the 
protruding  grape-like  small  lymphocytes.  The  red  corpuscles, 


208      THE    PROTEOMORPHIC   THEORY   AND   THE    NEW    MEDICINE 

meantime,  tended  to  take  a  coppery  stain.  Many  of  them  were 
conspicuously  vacuolated,  and  a  few  showed  faint  neuclei. 

But  whereas  the  mononuclear  leucocytes  of  these  two  very 
distinct  types  sprinkled  every  field  of  the  microscope  so  thickly 
as  almost  to  compete  with  the  red  corpuscles,  it  was  necessary  to 
search  across  a  large  number  of  fields  in  succession  before  finding 
a  single  polynuclear.  Now  and  again,  however,  one  did  appear ; 
and  the  character  of  this  rare  exhibit  was  altogether  unequivocal. 
The  nucleus  was  usually  of  bizarre  type,  but  distinct  and  clearly 
defined ;  and  there  was  a  normal  quantity  of  clear  cytoplasm.  In 
running  clear  across  the  smear,  one  might  come  upon  a  single 
polynuclear,  or  two  or  three  at  most ;  but  at  the  very  end  of  the 
smear,  in  a  dense  windrow,  one  might  find  a  mass  of  cells  many 
of  which  had  the  appearance  of  being  degenerated  polynuclears. 
Their  structure,  to  be  sure,  was  ill  defined ;  their  seemingly 
nuclei  were  jumbled  and  as  it  were  compacted;  and  they  were 
crowded  together  in  such  fashion  that  no  trace  of  distinct  cyto- 
plasm remained.  These  cells  took  the  stain  faintly,  like  the  large 
monocytes  already  referred  to ;  yet  they  showed  traces  of  nuclear 
structure  not  to  be  seen  in  the  large  monocyte,  and  one  felt  that 
they  were  of  a  different  type.  These  cells  did  not  appear  in  the 
earlier  smears ;  and  I  am  led  to  question  whether  perhaps  their 
presence  suggests  a  tendency  to  restocking  of  the  blood  with  the 
hitherto  minimized  neutrophiles. 

It  is  further  notable  that  in  the  most  recent  smear  I  detected 
a  single  gigantic  eosinophile,  with  three  discrete  nuclei,  the  cyto- 
plasm abundant  and  sharply  defined,  and  taking  a  brick-red  color, 
the  individual  granules  very  small.  In  this  most  recent  smear, 
also,  there  appeared  to  be  larger  numbers  of  large  monocytes 
that  show  a  fairly  distinct  nucleus  differentiated  from  the  cyto- 
plasm. The  total  number  of  the  large  monocytes,  as  contrasted 
with  the  lymphocytes,  has  also  conspicuously  increased.  In  a 
single  field  of  the  microscope,  for  example,  using  the  1.9  milli- 
meter objective  and  Number  10  eyepiece,  and  further  minimizing 
the  field  by  lengthening  the  tube,  the  count  showed  fifteen  small 
lymphocytes  and  twenty-one  large  monocytes,  with  not  far  from 
one  hundred  red  corpuscles.  Another  field  showed  only  eight 
small  lymphocytes  and  twenty-three  large  monocytes.  Such  a 
preponderance,  however,  was  unusual ;  and  fields  could  be  found 
where  the  relative  numbers  were  reversed.  Thirty  fields  in  suc- 
cession revealed  only  a  single  polynuclear. 

The  total  leucocyte  count  at  this  time  is  1,048,000,  as  against 
a  red-cell  count  of  2,324,000.  Yet  it  is  an  astonishing  fact  that 
this  patient,  aside  from  the  still  noticeable  enlargements  at  the 
sides  of  the  neck  (which,  however,  are  no  longer  extremely  con- 
spicuous), might  readily  pass  under  fairly  close  inspection  as  a 


THE    SCIENCE    AND   ART   OF    PROTEAL   THERAPY  209 

man  with  the  appearance  of  robust  health.  His  skin  has  a  good 
healthy  glow,  his  actions  are  vigorous  and  energetic;  and  he 
reports  himself  as  feeling  exceedingly  well.  His  appetite  is  so 
good  that  he  has  to  curb  it  to  prevent  overeating ;  he  sleeps  well 
(although  obliged  to  get  up  several  times  to  empty  the  bladder, — 
the  urine,  however,  showing  no  abnormality  on  analysis)  ;  and 
he  is  able  to  perform  fairly  vigorous  labor,  such  as  wood-sawing, 
shoveling  snow,  and  the  like,  and  in  general  to  execute  the  duties 
incident  to  keeping  his  modest  country  establishment  in  order, 
without  experiencing  shortness  of  breath  or  undue  fatigue.  His 
pulse,  during  his  visits  at  my  office,  has  ranged  from  72  to  80; 
and  the  blood  pressure  from  145  to  130, — a  fairly  characteristic 
reduction  under  Proteal  treatment.  In  a  word,  the  clinical  symp- 
tom-complex is  that  of  a  man  substantially  normal,  well  pre- 
served, and  more  than  moderately  active  and  robust  for  his  age. 

All  this,  it  will  be  observed,  with  a  total  corpuscular  count  of 
about  three  and  a  third  millions,  of  which  leucocytes  comprised 
more  than  a  million;  leaving  (according  to  the  most  recent 
count)  only  2,324,000  erythrocytes ;  and  providing  a  haemoglobin 
index  of  70. 

Incidentally,  I  may  suggest  that  the  fact  that  this  patient 
appears  not  to  suffer  in  the  least  from  lack  of  oxygenation  of  the 
tissues  gives  strong  support  to  the  Proteomorphic  thesis  that  the 
full  normal  equipment  of  red  corpuscles  is  by  no  means  necessary 
for  the  carrying  of  oxygen ;  for  of  course  it  is  not  to  be  supposed 
that  the  leucocytes  can  compensate  the  red  corpuscles  in  this 
regard ;  moreover,  even  if  they  were  able  to  do  so  (no  such  sug- 
gestion is  made),  the  total  number  of  corpuscles  is  still  not  much 
above  three-fifths  of  the  normal.  However,  cases  of  other 
types  are  common  enough  in  which  an  erythrocytic  equipment  of 
3,000,000  or  even  2,000,000,  suffices  to  oxygenate  the  tissues. 

The  anomaly  is,  that  the  universal  processes  of  food  hydrolysis 
and  of  bodily  metabolism  in  general  in  this  case  have  been  carried 
out  for  a  term  of  years  with  a  corpuscular  equipment  so  strangely 
maladjusted. 

But  the  mystery  is  to  some  extent  clarified  if  we  accept  the 
general  thesis  of  the  Proteomorphic  theory  and  the  special  inter- 
pretation of  that  thesis  just  elaborated,  according  to  which  the 
functions  of  the  different  types  of  leucocytes  overlap  or  are 
complementary,  permitting  what  might  be  described  as  team 
work,  through  which  weakness  in  one  leucocytic  department  may 
be  effectively  compensated  in  another ;  and  that  similar  team  work 
is  possible  between  the  white  corpuscles  and  the  red,  as  regards 
the  proteolytic  functions  of  the  latter. 

These  theoretical  assumptions,  considered  in  the  light  of  such  a 
case  of  lymphatic  leukaemia  as  that  just  recorded,  give  us  at  least 


210     THE   PROTEOMORPHIC  THEORY   AND  THE   NEW    MEDICINE 

suggestive  clues  as  to  the  origin  of  this  obscure  disorder.  A 
tenable  hypothesis  would  appear  to  be  that  degenerative  changes 
had  taken  place  in  the  particular  cells  of  the  bone  marrow  that 
normally  produce  polynuclear  leucocytes;  involving  also,  to  a 
less  extent,  associated  mother-cells  of  the  erythrocytes.  To 
meet  this  deficiency,  unusual  cohorts  of  small  lymphocytes  were 
called  into  action;  and  as  the  need  persisted,  and  was  perhaps 
progressively  aggravated  with  progressive  degeneration  of  the 
cytogenic  apparatus  in  the  bone  marrow,  there  was  hyperplasia 
of  the  entire  lymphatic  system  (roughly  analogous  to  the  compen- 
satory hypertrophy  of  heart  muscles  to  maintain  an  obstructed 
circulation),  of  which  tangible  evidence  was  given  in  the  observ- 
able enlargement  of  the  lymphatic  glands  in  many  regions. 

Observation  of  the  smear  before  Proteal  treatment  was  admin- 
istered, taken  in  connection  with  the  clinical  symptoms,  appears 
to  justify  the  inference  that  small  lymphocytes  in  superabundance 
may  on  occasion  perform  the  totality  of  leucocytic  labors  plus 
a  certain  amount  of  the  work  of  the  red  cells,  maintaining  a  fair 
semblance  of  normal  bodily  metabolism. 

It  would  appear  that  the  Proteals  stimulated  the  mother-cells 
of  the  large  monocytes  effectively,  and  that  these  cells  were  able 
to  take  the  work  off  the  small  lymphocytes  to  such  an  extent  that 
the  enlarged  lymphatic  glands  could  be  reduced ;  such  reduction 
being  perhaps  facilitated  by  direct  activities  of  the  large  mono- 
cytes, as  has  been  repeatedly  observed  in  cases  showing  malignant 
metastatic  involvement  of  the  lymphatics. 

The  appearance  of  increased  numbers  of  polynuclears,  albeit 
in  an  embryonic  or  degenerative  condition,  suggests  that  possibly 
the  Proteals  have  been  able  to  stimulate  to  some  extent  the  ex- 
hausted mother-cells  of  this  type  of  leucocytes.  Such  stimula- 
tion has  apparently  not  been  very  effective  hitherto,  however,  and 
the  stimulus  to  the  mother-cells  of  the  erythrocytes  has  seemingly 
been  even  less  effective,  since  the  number  of  these  cells,  although 
fluctuating  (at  one  time  reaching  3,400,000),  has  on  the  whole 
failed  to  increase.  It  should  be  remarked,  however,  that  the 
possibilities  of  Proteal  stimulation  in  this  direction  have  been 
by  no  means  exhausted ;  inasmuch  as  the  dose  administered  has 
not  been  increased  above  eight  minims.  The  treatment  has  been 
carried  out  under  somewhat  disadvantageous  circumstances,  the 
patient  coming  to  my  office  only  occasionally,  and  in  the  main  de- 
pending upon  home  administration.  Moreover,  it  has  been 
thought  well  to  advance  cautiously  in  view  of  the  extraordinary 
blood  conditions  to  be  dealt  with. 

Fuller  history  of  the  case  awaits  later  presentation ;  I  have 
dwelt  on  it  here  because  of  the  interesting  sidelights  that  it  throws 
on  the  Proteomorphic  theory,  and  because  of  the  conspicuous 


THE   SCIENCE   AND  ART   OF   PROTEAL  THERAPY  211 

clinical  betterment  that  attended  the  use  of  the  Proteals  in  a 
case  well  calculated  to  puzzle  the  therapeutist.  All  questions 
of  blood  picture  aside,  the  progress  of  the  case,  as  viewed  from 
the  patient's  standpoint,  has  been  exceedingly  gratifying.  Paro- 
tid glands  that  constituted  a  conspicuous  deformity  have  been 
reduced  to  less  than  half  the  original  size,  ceasing  to  be  very 
unpleasantly  noticeable;  lymphatic  nodules  larger  than  hickory 
nuts  have  been  reduced  to  the  vanishing  point;  persistent  pain 
in  connection  with  these  enlargements  has  totally  disappeared, 
without  recurrence  up  to  the  present,  and  the  patient's  general 
health,  though  never  greatly  impaired,  has  been  raised  to  a 
higher  level  of  seeming  vitality,  while  the  sense  of  well-being 
has  naturally  increased  with  the  vanishing  of  pain. 

STUDYING  THE  BLOOD  SMEAR 

I  have  a  few  additional  suggestions  to  make  as  to  compen- 
satory relations  of  the  different  types  of  leucocytes  versus  the 
army  of  erythrocytes ;  but  before  going  on  to  these,  I  would 
like  to  call  attention  to  certain  practicalities  of  the  study  of  the 
blood  smear  that  are  highly  essential  if  one  is  to  gain  a  really 
accurate  knowledge  of  the  actual  conditions  which  the  smear 
is  capable  of  revealing.  This  section  can  have  no  great  interest 
for  any  one  who  does  not  work  with  the  microscope,  but  I  be- 
lieve it  will  be  found  to  have  genuine  importance  by  a  good 
many  observers  who  regard  themselves  as  accomplished  students 
of  microscopical  blood  conditions.  Experience  has  taught  me 
that  some  very  elementary  considerations  in  the  study  of  the 
smear  are  often  overlooked,  and  that  skilful  hematologists  may 
employ  methods  of  making  the  differential  count  that  necessarily 
vitiate  or  invalidate  their  results. 

It  is  a  not  uncommon  error,  for  example,  as  a  good  many 
smears  sent  me  for  examination  show,  to  use  too  large  a  drop 
of  blood,  so  that  the  smear  runs  off  the  end  of  the  slide.  Differ- 
ential results  are  entirely  vitiated  in  such  a  case,  if,  as  often 
happens,  the  white  corpuscles  have  an  agglutinative  quality  and 
thus  tend  to  clump  at  the  end  of  the  smear — since,  in  this  case, 
the  end  of  the  smear  will  be  altogether  lacking.  It  is  impossible, 
in  such  a  case,  to  gain  more  than  a  vague  notion  of  the  true 
character  of  the  differential  count  from  the  most  careful  exam- 
ination of  the  smear.  The  data  for  an  accurate  accounting  are 
absolutely  lacking. 

Assuming,  however,  that  the  smear  is  properly  made,  the  entire 
content  of  the  drop  placed  on  the  slide  being  available  for  obser- 
vation, it  is  still  possible  to  examine  it  in  such  a  way  as  to 
draw  entirely  unwarranted  conclusions  as  to  the  differential  leu- 


212      THE    PROTEOMORPHIC   THEORY    AND   THE    NEW    MEDICINE 

cocytic  relations.  I  have  known  an  observer,  for  example,  to 
make  the  count  by  running  up  and  down  the  field,  thus  taking 
in  cross  sections,  instead  of  working  backward  and  forward 
laterally  along  the  entire  length  of  the  smear.  A  moment's  con- 
sideration makes  it  clear  that  if  the  leucocytes  are  not  evenly 
spread  on  the  smear,  such  a  method  may  give  a  record  that 
quite  negatives  the  facts. 

It  is  true  that  strictly  normal  blood  may  show  a  fairly  even 
distribution  of  the  different  types  of  leucocytes  at  different  stages 
of  the  smear.  But  the  distribution  is  probably  never  absolutely 
uniform,  and  with  the  blood  of  a  patient  suffering  from  a  pro- 
tein toxaemia  of  any  type  there  is  likely  to  be  the  most  striking 
unevenness.  Not  infrequently  the  small  lymphocytes  are  nearly 
all  left  near  the  beginning  of  the  smear,  whereas  the  polynu- 
clears  and  large  lymphocytes,  and  in  particular  the  large  mono- 
cytes,  are  dragged  along  toward  the  end  of  the  smear.  In  such 
a  case  the  result  of  a  cross-section  examination  (up  and  down 
the  field  as  the  examiner  views  it,  instead  of  from  side  to  side), 
will  depend  very  largely  upon  the  particular  point  that  chances 
to  be  brought  under  observation.  If  the  survey  is  made  near  the 
beginning  of  the  smear,  the  report  will  show  a  tremendous  pre- 
ponderance of  small  lymphocytes,  if,  on  the  other  hand,  it  is 
made  near  the  end  of  the  smear,  there  will  be  a  corresponding 
preponderance  of  polynuclears  or  large  monocytes.  In  either 
case,  the  accounting  is  worse  than  worthless ;  it  conveys  an  en- 
tirely wrong  impression  of  the  facts. 

But  the  difficulties  of  such  a  case  are  not  entirely  solved  merely 
by  making  the  lateral  survey.  It  is  true  that  such  a  survey  will 
put  one  on  the  trail  of  the  different  types  of  leucocytes  and  will 
ultimately  bring  all  types  into  the  field,  whether  they  have  stopped 
at  the  beginning  of  the  smear  or  have  been  carried  to  its  extrem- 
ity— provided,  of  course,  that  the  entire  length  of  the  smear  is 
examined.  But  a  point  I  have  never  seen  emphasized  is  that, 
quite  obviously — when  your  attention  is  called  to  it — you  do  not 
get  an  accurate  record  if  you  discontinue  counting  while  in  the 
midst  of  the  smear.  It  is  perfectly  clear  that  such  is  the  case, 
if  you  are  going  once  across  the  smear  only,  since  in  that  case 
you  may  not  have  come  to  the  portion  of  the  smear  that  contains 
the  chief  bulk,  of,  let  us  say,  the  large  monocytes.  But  a  mo- 
ment's reflection  will  make  it  clear  that  if,  after  going  across 
the  smear,  you  turn  about,  in  the  regular  way,  and  proceed  in 
the  reverse  direction,  you  must  now  go  clear  back  to  the  begin- 
ning of  the  smear,  else  you  will  not  give  proper  enrollment  to 
the  small  lymphocytes  that  were  largely  left  near  the  bginning. 

However  often  you  repeat  the  process,  you  must  never  stop 
short  of  a  complete  traversing  of  the  smear,  if  you  are  to  give 


THE   SCIENCE   AND  ART  OF   PROTEAL  THERAPY  213 

proper  enrollment  to  the  differently  distributed  types  of  leu- 
cocytes. 

Yet  I  venture  to  surmise  that  nine  observers  out  of  ten  dis- 
regard this  truism,  and  ultimately  stop  their  count  when  they 
have  registered  an  arbitrary  number  of  corpuscles,  say  two  hun- 
dred or  three  hundred,  regardless  of  the  fact  that  the  field  with 
which  they  abandon  the  count  may  lie  at  the  middle  of  the  smear. 

If  the  smear  is  a  short  one,  so  that  a  good  many  tours  have 
been  required  to  make  up  the  requisite  count  of  two  hundred  or 
three  hundred,  the  miscalculation  will  not  be  very  notable,  but 
if  a  long  smear  is  under  observation,  or  if  there  is  a  marked 
leucocytosis,  so  that  only  two  or  three  sweeps  of  the  smear  are 
necessary  to  complete  the  count,  the  inaccuracy  may  be  highly 
significant.  Smears  are  not  infrequent,  for  example,  in  which 
practically  all  small  lymphocytes  are  in  the  first  half  and  prac- 
tically all  the  large  monocytes  in  the  second  half.  If,  now,  the 
sweep  of  the  field  begins  at  the  beginning  of  the  smear,  and  two 
and  a  half  tours  of  the  field  are  required,  the  region  of  the 
small  lymphocytes  will  have  been  traversed  three  times,  whereas 
that  of  the  large  monocytes  will  have  been  traversed  only  twice, 
and  the  record  will  show  a  seeming  preponderance  of  small 
lymphocytes  in  excess  of  the  actuality — somewhat  in  the  ratio 
of  three  to  two.  But  if,  contrariwise,  three  and  a  half  tours 
of  the  field  were  required,  then  we  shall  have  traversed  the  region 
of  the  large  monocytes  four  times  and  the  regions  of  the  small 
lymphocytes  only  three  times,  and  the  record  will  show  a  ficti- 
tious preponderance  of  large  monocytes. 

In  a  word,  where  the  method  is  employed — and  it  is  almost 
universal — of  counting  a  definite  number  of  leucocytes,  it  can 
occur  only  in  the  exceptional  instances  where  the  count  happens 
to  be  finished  at  the  extremity  of  the  field,  that  the  result  is  as 
accurate  as  it  might  be  and  should  be.  The  degree  of  error  will 
vary  with  the  length  of  the  smear  (a  short  smear  being  pref- 
erable) and  with  the  aggregate  number  counted;  the  larger  the 
number,  naturally,  the  closer  approximation  to  accuracy.  But 
the  method  is  inherently  faulty  and,  in  my  opinion,  should  be 
abandoned. 

The  only  correct  way  to  make  the  differential  count,  as  I  see 
it,  is  to  work  clear  across  the  field  from  right  to  left  and  from 
left  to  right,  several  times,  preferable  at  considerable  longi- 
tudinal intervals,  so  that  in  the  end  practically  the  entire  area 
of  the  smear  has  been  sectioned,  and  to  stop  counting,  not 
when  an  arbitrary  number  has  been  reached,  but  at  the  end  of 
a  complete  tour  across  the  smear,  whether  that  tour  be  the  first 
or  the  twentieth.  A  single  or  double  sweep  across  the  field,  with 
an  aggregate  count  of,  let  us  say  137  leucocytes,  would  be,  in 


214      THE   PROTEOMORPHIC   THEORY   AND  THE    NEW    MEDICINE 

my  opinion,  more  accurate  in  its  results,  particularly  where  a 
long  smear  is  in  question,  than  an  arbitrary  count  of  200  or 
even  of  300  cells;  although,  of  course,  it  is  not  open  to  dis- 
pute that,  other  things  being  equal,  the  larger  the  count  the  closer 
the  approximation  to  accuracy.  Other  things  are  not  equal  in 
the  supposititious  cases  in  question. 

The  method  of  counting  an  arbitrary  even  number  of  cells 
has  nothing  whatever  to  recommend  it  except  ease  in  computing 
percentages.  Every  other  advantage  lies  with  the  method  of 
counting  clear  across  the  field,  letting  the  aggregate  number  be 
what  it  may  (but  continuing,  of  course,  until  the  aggregate  is 
reasonably  large),  and  the  additional  labor  of  computing  per- 
centages with  this  method  should  not  weigh  for  a  moment  against 
the  enhanced  value  of  the  results. 

INTESTINAL  TOXEMIAS  AND  THE  CORPUSCULAR  BALANCE 

Turning  now  from  this  parenthetical  excursion  into  the  region 
of  microscopic  technique,  which  I  trust  was  not  altogether  un- 
warranted, let  us  make  further  examination  of  the  corpuscular 
balance,  with  particular  reference  to  the  response  to  protein 
invasions  from  the  intestinal  tract.  Let  me  say  at  once  that 
the  observations  of  the  blood  falling  within  this  classification 
are  likely  to  be  very  discordant.  We  have  considered  cases  in 
which  intestinal  toxaemia  was  associated  with  very  pronounced 
leucocytosis.  There  are  other  cases  in  which  there  is  a  pro- 
nounced leucopcenia.  Sometimes,  at  least,  the  conflicting  evi- 
dence may  be  reconciled  by  considering  the  degree  of  chronicity 
of  the  cases  involved ;  recalling  that  habitual  stimulation  of  the 
cytogenic  apparatus  throughout  a  long  period  may  lead  to  exhaus- 
tion. I  have  records  of  several  cases  of  rheumatoid  arthritis, 
of  many  years'  standing,  in  which  the  outstanding  feature  of  the 
blood  count  is  a  conspicuous  paucity  of  leucocytes.  Usually  with 
these  cases  there  is  a  history  of  life-long  tendency  to  constipa- 
tion, associated  with  habitual  over-indulgence  in  proteid  foods. 

Presumably,  in  these  cases  at  an  early  stage,  there  was  over- 
stimulation  of  production  of  leucocytes  to  meet  the  protein  inva- 
sion. Exhaustion  has  followed,  and  the  leucocytes,  performing 
their  functions  inadequately,  have  put  an  excessive  burden  on 
the  red  corpuscles.  In  general  the  erythrocytes  have  appeared 
able  to  meet  in  some  measure  the  recurring  emergency,  as  shown 
by  their  relatively  large  numbers,  but  the  inadequacy  of  their 
ultimate  action  is  evidenced  in  the  incomplete  metamorphosis 
and  elimination  of  protein  end  products,  in  particular  uric  acid. 
The  weak  spot  in  the  heredity  armor  of  the  individual  being  the 
fibrous  tissues  and  serous  membranes  of  the  joints,  deposits  of 


THE   SCIENCE  AND  ART  OF  PROTEAL  THERAPY  215 

urates  occur  here,  with  the  gradual  development  of  the  char- 
acteristic malformations  of  chronic  arthritis. 

There  is  nothing  in  these  end-product  deposits  to  give  new 
stimulus  to  the  mother-cells  of  the  leucocyte.  The  case  is  differ- 
ent, however,  with  an  individual,  who,  with  the  same  aetiological 
conditions,  as  to  protein  invasion,  has  an  hereditary  predisposi- 
tion to  hyperplasia  of  cells  under  stimulus  of  a  local  irritation 
which  may  lead  to  the  development  of  a  malignant  neoplasm. 

I  have  elsewhere  developed  the  thesis  (see  the  Monograph) 
that  the  essential  characteristic  of  malignancy  in  a  neoplasm 
is  that  its  cells  are  more  or  less  subject  to  proteolysis  by  the 
corpuscular  enzymes.  According  to  this  view,  the  cancer  cells, 
in  thus  undergoing  hydrolysis,  stimulate  the  blood-forming  mech- 
anisms and  lead  thus  to  leucocytosis,  and  in  particular  to  large 
monocytosis.  Whether  the  sequel  will  show  complete  hydrolysis 
and  elimination  of  the  cancer  cells  or  not  depends  upon  the  per- 
sistence of  the  local  irritative  stimulus,  the  degree  of  develop- 
ment of  the  cancer  cells  themselves,  the  responsiveness  of  the 
blood-forming  mechanism,  and  other  factors  that  do  not  here 
concern  us.  What  is  here  significant  is  that  one  does,  in  point 
of  fact,  find  a  leucocytosis,  and  a  relative  monocytosis,  as  the 
almost  constant  accompaniment  of  a  cancerous  invasion;  and 
that  the  stimulus  given  by  the  disintegrating  cancer  cells  them- 
selves may  be  supposed  adequately  to  explain  the  condition,  in 
contrast  with  the  leucopcenia  of  the  arthritic  patient  who  lacks 
this  stimulus.  But  I  repeat  that,  could  we  have  seen  the  arthritic 
patient  at  an  earlier  stage,  we  should  probably  have  found  that 
the  protein  invasion  (usually  from  the  intestines)  had  produced 
a  leucocytosis  that  long  persisted  before  exhaustion  of  the  cyto- 
genic  mechanism  came  about.  In  substantiation  of  this  view,  we 
not  infrequently  find  a  leucocytosis,  and  in  particular  a  notable 
large  monocytosis,  present  in  young  individuals  suffering  from 
intestinal  toxaemia,  in  whom  the  cytogenic  apparatus  is  still  re- 
sponsive. Moreover,  such  an  increase  has  been  observed  in  cases 
of  intestinal  toxaemia  that  have  not  undergone  proteal  treatment ; 
although  in  other  cases  of  this  type  (as  above  noted)  the  large 
monocyte  count  is  low. 

Here,  for  example,  is  a  man  of  26,  who  has  suffered  all  his 
life  from  intestinal  toxaemia.  So  poor  is  his  assimilation  that, 
even  when  in  best  condition,  he  is  almost  skeletal,  carrying  no 
excess  avoirdupois  whatever.  His  stomach  is  his  perpetual  en- 
emy. His  differential  count  shows  50  per  cent,  polynuclears, 
34.3  per  cent,  small  lymphocytes,  22  per  cent,  large  mononuclears, 
and  0.6  per  cent,  eosinophiles.  It  is  observed  that  the  small 
lymphocytes  are  mostly  relatively  large  and  with  abundant  cyto- 
plasm, so  that  one  is  constantly  tempted  to  classify  them  as  large 


216      THE   PROTEOMORPHIC   THEORY   AND  THE    NEW    MEDICINE 

lymphocytes;  yet  even  so  the  number  of  cells  registered  as 
unequivocal  small  lymphocytes  is  at  a  high  normal  limit.  Mean- 
time the  large  mononuclears,  which  are  seen  to  stain  deeply  and 
with  ill-defined  nuclear  bounds,  represent  22  per  cent,  of  the 
leucocyte  count,  a  proportion  seldom  observed  except  under  the 
stimulus  of  proteantigen  treatment.  The  nuclei  of  all  the  white 
cells  stain  very  poorly,  a  second  staining  with  methylene  blue 
being  required  to  bring  them  out  at  all  clearly. 

An  explanation  of  these  peculiarities,  consonant  with  the  hy- 
pothesis all  along  expounded,  would  be  that  in  this  case  sto- 
machic and  intestinal  digestion  are  so  defective  that  relatively 
large  numbers  of  unbroken  protein  molecules  find  their  way 
through  the  intestinal  walls.  This  invasion  is  met  by  a  large 
mononuclear  population,  and  in  particular  by  the  extraordinary 
aggregation  of  large  monocytes.  The  condition  here  is  strictly 
comparable  to  the  conditions  that  obtain  where  there  is  a  well- 
developed  cancer;  in  each  case  there  is  constant  intrusion  of 
fully  formed  proteins  into  the  circulation,  and  the  increase  in 
large  monocytes  shows  the  response  of  the  defensive  mechanism. 
The  relative  effectiveness  of  response  in  this  case  may  be  ex- 
plained, perhaps,  by  the  fact  that  the  patient  is  young  and  hence 
has  a  more  resilient  cytogenic  apparatus  than  the  average  cancer 
subject. 

The  particular  case  of  intestinal  toxaemia  in  question  is  known 
to  me  only  by  report  and  from  a  blood  smear  sent  to  me  from 
a  distance,  so  I  am  not  able  to  record  the  results  of  Proteal 
treatment,  which  would  be  of  obvious  interest.  I  have  had 
numerous  cases  of  intestinal  toxaemia  more  or  less  similar  to 
this,  however,  under  treatment,  and  I  am  able  to  report  that 
the  results  of  Proteal  treatment  have  in  most  instances  been 
as  satisfactory  as  the  theoretical  consideration  above  outlined 
might  lead  one  to  anticipate.  As  a  rule,  these  cases  do  not  have 
a  high  large  monocyte  count  at  the  outset,  presumably  because 
their  digestive  protein  products  are  at  an  intermediate  stage  of 
decompounding  before  they  penetrate  the  intestinal  walls.  The 
red  cells,  however,  whether  or  not  they  are  reduced  in  number,  are 
likely  to  show  very  marked  abnormalities  of  form,  suggestive 
of  perverted  function ;  and  the  white  cells,  frequently  increased 
in  number,  tend  to  take  the  stain  very  badly,  and  to  have  an 
agglutinative  quality  that  leads  to  their  clumping  and  assembling 
in  windrows  at  the  end  of  the  smear.  Very  commonly  the  red 
cells  in  the  Toisson  solution  show  a  large  proportion  of  small 
or  misshapen  cells,  battered  looking,  crenated,  or  covered  with 
spicular  pseudopodia,  giving  them  an  appearance  that  I  am  accus- 
tomed to  liken  to  that  of  a  miniature  sea  urchin.  There  may  be 


THE    SCIENCE   AND   ART   OF   PROTEAL   THERAPY  217 

curious  vacuolations  or  typical  modifications  of  the  structure 
giving  a  figured  appearance. 

All  these  things,  to  be  sure,  may  be  seen  more  or  less  in  rela- 
tively normal  blood  cells;  but  the  proportion  of  cells  showing 
such  aberrant  conditions  is  very  greatly  increased  in  cases  of 
intestinal  toxaemia,  particularly  when  associated  with  rheumatic 
sequels.  One  cannot  well  doubt  that  there  are  profound  chem- 
ical changes  in  both  red  and  white  cells  of  such  a  subject. 

A  typical  case  recently  under  treatment  is  that  of  a  young 
woman  whose  clinical  symptoms  included  "general  debility,"  poor 
circulation  associated  with  cold  hands  and  feet,  lack  of  appe- 
tite, lassitude  and  depression,  and  a  tendency  to  enlargement  and 
pain  of  the  finger  joints  of  "rheumatic"  character. 

The  blood  count  showed  3,571,000  red  corpuscles  of  character- 
istic abnormal  quality,  and  9,690  white  cells  of  the  faint-staining, 
clumping  variety.  The  polynuclears  represented  82.6  per  cent., 
small  lymphocytes  9.6  per  cent.,  the  large  mononuclear  7  per 
cent.,  and  the  eosinophiles  0.6  per  cent. 

After  three  weeks  of  Proteal  treatment  (Nos.  37  and  45  in 
doses  of  3  to  6  minims  on  alternate  days),  there  was  marked 
improvement  all  along  the  line  in  clinical  symptoms,  including 
conspicuous  change  in  the  patient's  appearance  and  feelings,  and 
the  blood  count  showed  more  than  6,000,000  red  cells  which  at 
first  seemed  normal,  but  afterward  became  picturesquely  modi- 
fied along  the  lines  just  referred  to.  The  white  cells  had  been 
reduced  to  5,800,  and  there  was  most  striking  modification  of 
the  differential  count,  which  now  showed  59.5  per  cent,  poly- 
nuclears, 26.5  per  cent,  small  lymphocytes,  and  14  per  cent,  large 
mononuclears.  Occasional  normoblasts  and  groups  of  platelets 
were  now  present.  A  modification  of  the  chemical  condition 
of  the  whites  was  suggested  in  the  fact  that  the  nuclei  now 
stained  deep  purple,  the  cytoplasm  being  markedly  acidophile. 
The  individual  leucocytes  were  large,  and  there  was  not  much 
clumping. 

This  patient,  obviously,  requires  a  long  course  of  proteal  treat- 
ment to  bring  about  permanent  modification  of  the  disturbances 
of  metabolism,  but  the  changes  effected  in  so  short  a  period  are 
striking  and  gratifying.  The  case  is  still  under  treatment. 

BY  WAY  OF  SUMMARY 

The  reader  of  the  Monograph  on  The  Proteal  Treatment  of 
Cancer  is  aware  that  the  theory  that  underlies  my  interpretation 
of  most  of  the  phenomena  of  protein  therapy  traces  a  large  part 
of  the  ills  of  middle  life  to  disturbances  of  protein  metabolism. 


218      THE   PROTEOMORPHIC  THEORY   AND  THE    NEW    MEDICINE 

It  will  be  recalled  that  I  listed  lymphatic  and  myologenous  leukae- 
mias and  pernicious  anaemia,  and  such  seemingly  diverse  con- 
ditions as  anaemic  obesity,  Graves'  disease,  arthritis,  arterio- 
sclerosis, and  neoplasms  of  all  types  under  a  common  heading 
as  evidence  of  the  "cancerous  condition."  The  detailed  expo- 
sition of  a  certain  number  of  typical  cases  in  recent  pages  has 
been  intended  to  illustrate  in  some  measure  the  validity  of  this 
classification.  In  my  original  exposition  of  the  principles  of 
protein  therapy,  so  often  referred  to  in  these  pages,  I  spoke  of 
the  proteantigen  response  as  applicable  to  all  types  of  protein 
infection.  The  present  entire  volume  is  but  an  elaboration  of 
that  thesis. 

It  is  perhaps  unnecessary  to  detail  further  individual  cases 
to  emphasize  the  opinion  that  disturbances  of  the  blood  grow- 
ing out  of  abnormal  alimentation  may  be  aetiologically  connected 
with  many  types  of  maladies  that  have  not  hitherto  been  asso- 
ciated in  the  mind  of  the  average  practitioner.  It  should  be 
axiomatic  to  say,  however,  that  abnormal  modifications  of  the 
blood  must  have  wide  and  various  implications  in  disturbed 
functionings  of  the  bodily  organs.  It  is  scarcely  too  much  to 
say  that  there  are  no  maladies  that  are  not  to  some  extent  asso- 
ciated with  disturbances  of  metabolism  that  must  register  them- 
selves in  the  blood,  whether  or  not  we  are  able  to  read  the  record. 

Every  practical  physician  knows  how  prevalent  are  anaemias 
of  various  types,  whether  or  not  associated  with  recognized 
sources  of  protein  infection.  But  the  manner  of  association — 
the  universality  of  disturbed  protein  metabolism  as  a  factor  in 
producing  anaemias — was  perhaps  never  so  adequately  explicable 
on  any  other  hypothesis  as  it  becomes  when  interpreted  in  the 
light  of  the  Proteomorphic  theory.  And  assuredly  there  is  no 
remedial  agent  hitherto  available  that  so  directly  and  so  explic- 
itly goes  to  the  source  of  disturbance  and  tends  to  correct  it  as 
do  the  proteantigens. 

It  will  be  a  little  difficult  for  the  profession  to  accustom 
itself  to  the  idea  that  the  same  line  of  treatment,  modified  to 
meet  individual  cases,  may  be  applicable  to  maladies  recorded 
under  such  diverse  headings  as  intestinal  toxaemias,  anaemias, 
arthritis,  psoriasis,  asthma,  tuberculosis,  and  cancer.  But  when 
the  idea  is  clearly  grasped  that  there  are  important  underlying 
causal  factors  that  are  the  same  for  all  these  conditions,  the 
logicality  of  the  protein  treatment  will  be  obvious. 

And  I  predict  with  much  confidence  that  the  practical  physi- 
cian, whatever  his  attitude  toward  theories  of  therapeutic  action, 
will  feel  that  Proteal  medication  places  in  his  hands  a  new 
weapon  of  unique  value  in  the  treatment  of  a  wide  range  of 
maladies  of  middle  life  and  old  age  that  hitherto  have  proved 


THE    SCIENCE   AND   ART   OF   PROTEAL   THERAPY  219 

intractable.  When  he  has  seen  the  blood  count  in  an  anaemic 
patient  change  more  radically  after  a  week  or  ten  days  of  treat- 
ment than  he  would  otherwise  have  been  able  to  change 
it  in  as  many  months,  he  will  come  to  recognize  the  Proteals  as 
indispensable  additions  to  his  equipment,  compared  with  which 
the  entire  list  of  specific  serums  and  vaccines  have  minor  sig- 
nificance. 

In  speaking  thus,  I  have  no  intention  to  disparage  the  value 
of  specific  serums  and  vaccines.  I  have  been  from  the  outset 
an  enthusiastic  advocate  of  these  methods.  I  have  only  in  mind 
the  thought  that  the  diseases  to  which  they  are  applicable  are 
relatively  rare;  whereas  the  maladies  herein  under  considera- 
tion, as  associated  with  disturbed  protein  metabolism  and  more 
or  less  amenable  to  Proteal  medication,  are  so  prevalent  that 
they  claim  by  death  three-quarters  of  a  million  individuals  in 
the  United  States  each  year.  I  think  it  is  not  quixotic  to  express 
the  belief  that  a  more  intelligent  application  of  dietetics  com- 
bined with  the  rational  use  of  Proteal  therapy  may  modify  very 
conspicuously  the  mortality  statistics  of  the  not-distant  future. 

I  bring  this  outline  of  the  development  and  present  status  of 
protein  therapy  to  a  close  with  a  full  sense  of  the  inadequacy  of 
the  presentation  that  has  been  given.  I  have  not  so  much  as 
referred  to  the  recent  literature  that  shows  how  actively  the 
minds  of  many  physicians  in  various  parts  of  the  world  are 
turning  toward  the  subject.  My  intention  throughout  has  been 
to  give  a  resume  of  the  pioneer  work  in  this  field;  my  own 
experience  and  the  experience  of  co-operating  physicians  still 
constituting,  no  doubt,  by  far  the  largest  body  of  evidence  in 
existence  as  to  the  therapeutic  use  of  non-specific  proteantigens. 
It  suffices  to  say  that  the  reports  that  have  come  from  a  number 
of  independent  workers  in  this  country  and  in  Europe  during 
recent  months,  although  covering  only  a  part  of  the  field  of  our 
researches,  have  been  singularly  corroborative  of  our  results.  In 
particular,  the  work  of  Miiller  and  Thanner  and  their  associates 
in  Berlin  in  the  use  of  milk  protein  and  an  "albumose  prepara- 
tion" in  the  treatment  of  infective  maladies  of  the  eye,  including 
those  of  syphilitic,  of  rheumatic,  and  of  gonorrheal  origin,  have 
peculiar  interest.  Such  extensions  of  the  method  will  excite 
no  surprise  in  any  one  who  has  grasped  the  principles  of  the 
therapeutic  action  of  the  proteantigens,  as  originally  detailed  in 
my  paper  of  October  2,  1915,  and  as  elaborated  throughout  this 
book.  Disturbed  protein  metabolism  underlies  a  great  variety 
of  maladies,  particularly  in  middle  life  and  old  age ;  and,  as  my 
original  presentation  stated,  protein  therapy  is  directed  "against 
all  protein  infections." 

Even   where   the   infection   is    specifically   bacterial   there   is 


220      THE   PROTEOMORPHIC  THEORY   AND  THE   NEW    MEDICINE 

theoretical  warrant  for  the  administration  of  agents  that  stim- 
ulate the  blood-forming  mechanism  to  effective  activity,  since 
"good  blood"  is  always  at  a  premium.  Moreover,  it  is  plausible 
to  suppose  that  when  the  cytogenic  apparatus  is  thus  rendered 
active,  its  functionings  will  result,  under  proper  stimulus,  in  a 
maximum  production  of  specific  anti-bodies  directed  against  the 
toxins  of  a  particular  bacterium,  as  well  as  of  general  enzymes 
to  deal  with  the  proteid  bodies  of  the  bacteria  themselves. 

It  appears  fairly  certain,  then,  that  the  range  of  application  of 
non-specific  protein  therapy  overlaps  the  field  of  specific  therapy, 
and  has  even  wider  connotations  than  those  included  in  the  prac- 
tical use  of  the  method  up  to  the  present.  Yet  even  as  the  case 
stands  at  the  moment,  protein  therapy,  of  proved  value  in  condi- 
tions ranging  from  anaemia  and  intestinal  toxaemia  to  typhoid 
fever  and  tuberculosis,  and  from  rheumatism  to  cancer — a 
method,  in  short,  that  combats  every  form  of  protein  toxaemia 
by  fortifying  the  bodily  defensive  and  offensive  mechanism  as 
represented  in  blood-forming  organs  and  blood  corpuscles — may 
without  exaggeration  be  said  to  constitute  the  most  general  and 
the  most  comprehensive  procedure  known  to  modern  scientific 
therapeutics. 

It  is  my  confident  belief  that  in  the  very  near  future  non- 
specific protein  therapy — and  in  particular  Proteal  therapy — will 
be  so  generally  employed  as  to  modify  the  mortality  statistics  of 
the  degenerative  diseases  of  middle  life  and  old  age  not  less 
conspicuously  than  the  mortality  of  diphtheria  has  been  modi- 
fied by  specific  serum  therapy  and  the  mortality  of  typhoid  fever 
by  the  anti-typhoid  vaccine.  In  its  ultimate  application,  Proteal 
therapy  will  find  a  prominent  place  among  preventive  measures 
and  in  the  incipiency  of  disorders  of  nutrition.  In  its  earliest 
application  to  the  later  stages  of  the  most  malignant  of  disorders 
of  disturbed  metabolism,  it  showed  astonishing  efficacy;  but  the 
full  measure  of  its  value  can  be  taken  only  when  it  is  generally 
used  to  counteract  disorders  of  nutrition  in  their  incipiency — 
simple  anaemias,  neurasthenias,  mild  autointoxications,  "run- 
down" conditions — or  at  a  stage  short  of  profound  cachexia  and 
permanently  degenerated  organs.  The  present  book  will  have 
served  its  purpose  if  it  arouses  the  profession  to  a  realization  of 
the  enheartening  possibilties  along  these  lines  now  made  available 
by  protein  therapy  in  its  wider  aspects. 


PART  II 

CANCER:    INTERPRETED  IN  THE  LIGHT  OF  THE 

PROTEOMORPHIC    THEORY   AND    THE 

PROTEIN    RESPONSE 

The  ensuing  pages  reproduce  with  occasional  modifications  about 
two-thirds  of  the  text  of  the  Monograph  so  frequently  referred  to  in 
this  book,  as  published  December  i,  1916,  under  title  of  The  Pro- 
teal  Treatment  of  Cancer  and  Allied  Conditions:  A  Practical  Study 
of  a  New  Therapeutic  Principle  as  Interpreted  in  the  Light  of  the 
Proteomorphic  Theory. 

•     I  have  thought  that  it  might  be  of  historical  interest  to  include 
the  dedication  of  that  work,  which  is  therefore  reproduced  overleaf. 


mmtograpl) 

telling  or  a  humanitarian  work  that  vitally  concerns  the  lives 
and  welfare  of  one-sixteenth  of  the  world's  total  popula- 
tion,— a  work  carried  forward  in  the  face  of  fanatical  op- 
position, under  almost  insuperable  difficulties,  and  at  great 
personal  sacrifice, — • 

(0  DcDf CfltcD 

to  the  memory  of  five  of  my  New  England  ancestors — 
representing  four  patronymic  generations  in  direct  line — 
who  were  Regular  physicians  of  distinction,  namely: 

(i)  My  great  great  grandfather  ^  THOMAS  WILLIAMS, 
A.M.  (Yale),M.D.  (1718-1775), Colonial  surgeon  in  the 
French  and  Indian  wars  and  brother  of  the  founder  of 
Williams  College;  my  great  grandfathers  (2)  WILLIAM 
STODDARD  WILLIAMS,  M.D.  (1762-1828),  of  Deer- 
field,  Mass.,  and  (3)  JOSEPH  GOODHUE,  M.D.,  of  Ports- 
mouth, surgeon  in  the  Federal  Army;  (4)  my  grandfather, 
STEPHEN  WEST  WILLIAMS,  A.M.,  M.D.  (1790-1856), 
Professor  and  Lecturer  upon  Medical  Jurisprudence,  the 
Theory  of  Medicine,  and  Medical  Botany,  in  the  Berkshire 
Medical  Institute,  in  the  College  of  Physicians  and  Surgeons 
in  New  York,  in  Dartmouth  College,  and  in  Willoughby 
University;  author  of  numerous  books;  personal  friend  of 
Valentine  Mott  and  Oliver  Wendell  Holmes ;  close  associ- 
ate of  N.  S.  Davis  in  the  organization  of  The  American 
Medical  Association;  and  (5)  EDWARD  JENNER  WILLIAMS, 
M.D.  (1823-1881),  my  father,  a  man  endowed  with  rare 
qualities  of  mind  matched  by  yet  rarer  qualities  of  heart: 

Each  of  them  perennially  active  in  the  service  of  human- 
ity; each  of  them  in  the  forefront  of  the  medical  progress 
of  his  time;  each  of  them  a  life-long  zealot  for  the  best 
traditions  of  medical  ethics;  each  of  them  honored  by  all 
who  knew  him  in  life,  and  in  death  epitaphed  simply  and 
justly  with  the  words: 

"He  was  a  skillful  practitioner  and  an  honest  man." 


PART  II 

CANCER:    INTERPRETED  IN  THE  LIGHT  OF  THE 

PROTEOMORPHIC  THEORY  AND  THE 

PROTEIN  RESPONSE 

SECTION  I 
THE  NATURE  OF  CANCER 

In  the  paper  of  October  2,  1915,  in  the  New  York  Medical 
Journal,  I  suggested  the  following  definition  and  interpretation 
of  cancer: 

One  might  define  cancer,  in  the  light  of  the  present  theory, 
as  a  systemic  condition  characterized  by  the  development  of 
neoplastic  cells  of  a  somewhat  embryonic  type,  in  conjunction 
with  an  excess  of  leucocytes  in  the  blood  and  a  deficiency  [actual 
or  relative]  of  red  blood  corpuscles. 

It  must  further  be  postulated  that  the  neoplastic  cells  are  of  a 
type  susceptible  to  the  attacks  of  leucocytic  enzymes,  so  that  there 
is  a  constant  tendency  to  disintegration  of  some  of  these  cells 
under  the  attacks  of  the  white  blood  corpuscles.  Meanwhile,  the 
deficiency  [actual  or  relative]  in  red  blood  corpuscles  makes  it 
impossible  for  the  system  to  deal  adequately  with  the  partially 
hydrolyzed  protein  products  resulting  from  the  breaking  down 
of  some  of  the  new  cells  under  the  attacks  of  the  leucocytes. 
The  net  result  is  a  condition  of  protein  poisoning  or  autointoxi- 
cation which,  when  fully  developed,  constitutes  the  characteristic 
"cancer  cachexia,"  and  ultimately  causes  the  death  of  the  patient. 

It  should  be  observed  that  this  new  definition  of  cancer  explains 
the  hitherto  obscure  fact  that  almost  any  kind  of  new  growth 
in  the  organism  may  on  occasion  take  on  the  characteristics  of 
malignancy.  A  fibroid  tumor  of  the  uterus,  for  example,  is  not 
ordinarily  "malignant"  because  its  tissues  are  of  a  type  that  the 
leucocytic  enzymes  cannot  readily  attack — largely,  perhaps,  be- 
cause of  their  slow  development  and  firmness  of  texture.  Yet 
on  occasion,  as  is  well  known,  portions  of  a  fibrous  growth  may 
become  susceptible  to  disintegration  under  the  attacks  of  the 
bodily  enzymes ;  and  in  such  a  case,  should  the  red  blood^  cor- 
puscles fail  of  their  appointed  task,  a  condition  of  veritable 
malignancy  is  attained,  and  the  aforetime  fibroid  becomes  a 
cancer. 

Ordinarily,  however,  the  neoplastic  growth  is  from  the  outset 
composed  of  such  cells  as  are  more  or  less  susceptible  to  the 

223 


224  THE  PROTEAL  TREATMENT  OF  CANCER 

action  of  the  leucocytes;  and,  from  a  pathological  standpoint, 
it  is  permissible  to  regard  all  such  growths  as  nascent  cancers. 
In  a  vast  majority  of  cases,  however,  the  neoplasm  is  denied 
opportunity  of  considerable  growth,  because  of  the  immediate 
attacks  of  the  leucocytes,  which  are  backed  up  by  the  erythrocytes 
to  such  good  effect  that  the  neoplastic  proteins  are  completely  dis- 
sociated and  eliminated  from  the  body  without  producing  harmful 
results,  and,  indeed,  as  a  rule,  without  being  given  any  considera- 
tion whatever. 

It  is  probable  that  there  -are  scores  of  nascent  neoplasms  that 
are  dissociated  and  obliterated  for  every  one  that  attains  mastery 
over  the  corpuscular  bodily  defenders  and  becomes  a  tangible 
neoplasm.  It  is  probable,  in  other  words,  that  every  insignificant 
lesion  of  the  bodily  tissues  that  calls  for  the  development  of  new 
cells  in  the  process  of  repair,  might  be  regarded  as  an  incipient 
malignant  neoplasm;  and  is  prevented  from  becoming  an  actual 
menace  only  by  the  efficient  activities  of  the  corpuscles  that  are 
normally  present  in  adequate  numbers  for  the  bodily  defense. 

In  elaboration  of  the  idea  underlying  this  conception  of  can- 
cer, I  now  suggest  the  following  expanded  definition : 

Hyperproteomorphism,  or  the  Cancerous  Condition,  is  a  sys- 
temic condition  characterized  by  a  profound  disturbance  of  pro- 
tein metabolism  involving  originally  the  blood  and  blood-forming 
mechanism ;  evidenced  by  disturbances  of  the  corpuscular  balance 
and  the  abnormal  proliferation  of  cells  of  one  type  or  another; 
frequently,  but  not  necessarily,  associated  sequentially  with  local 
neoplasms  comprising  cells  that  are  partly  subject  to  hydrolysis 
under  influence  of  the  enzymes  developed  by  the  white  and  red 
corpuscles. 

As  elaborating  the  definition,  I  suggest  the  following  classifi- 
cation of  the  varied  manifestations  of  the  cancerous  condition: 

(1)  Lymphatic  and  Myelogenous  Leukaemias  and  Pernicious 
Anaemia,    where    the    hyperplasia    involves    the    blood-forming 
tissues. 

(2)  Anaemic  obesity,  characterized  by  excessive  fat-founda- 
tion and  deposit,  at  the  expense  of  more  useful  tissues. 

(3)  Proteoid  hypertrophy,  as  in  Grave's  Disease  and  myxoe- 
dema,  where  the  lawless  new  growth  involves  glandular  and 
lymphatic  tissues. 

(4)  Chronic  rheumatoid  arthritis,  where  the  maladjustment 
of  metabolism  manifests  itself  in  a  tendency  to  new  growths  in 
connection  with  the  cartilage  of  the  joints. 

(5)  Arterio-sclerosis,  where  the  localized  evidence  of  nutri- 
tional  maladjustment   involves   the   tissues   of   the   circulatory 
apparatus. 

(6)  Benign  neoplasms,  where  a  local  irritation  in  association 
with  the  disturbance  of  protein  metabolism  has  led  to  a  prolifer- 


THE  ORIGIN  OF  CANCER  225 

ation  of  localized  tissues  not  freely  subject  to  proteolysis  by  the 
corpuscular  enzymes. 

(7)  Malignant  neoplasms,  or  true  cancer,  where  a  localized 
irritation  or  abrasion  has  cooperated  with  protein  maladjustments 
to  cause  a  proliferation  of  epithelial,  endothelial,  or  connective 
tissues  constituting  a  more  or  less  conspicuous  neoplasm  the  tis- 
sues of  which  are  to  some  extent  subject  to  hydrolysis  by  the 
corpuscular  enzymes.  Here  the  development  of  the  neoplasm 
in  itself  evidences  the  disturbed  conditions  of  protein  metabolism 
in  the  body  (deficiency  of  corpuscular  enzymes),  and  the  new 
cells  tend  further  to  disturb  that  maladjustment  by  presenting 
additional  protein  material  for  hydrolysis. 

I  am  fully  cognizant  that  so  revolutionary  a  definition  and 
classification  as  the  above,  in  which  it  is  suggested  that  the  can- 
cerous condition  is  not  necessarily  associated  with  the  presence 
of  such  a  neoplasm  as  is  commonly  supposed  to  constitute  the 
essentials  of  the  disease,  must  excite  surprise  and  opposition.  But 
I  venture  to  believe  that  the  more  closely  the  matter  is  consid- 
ered, the  more  valid  will  seem  the  reasoning  on  which  the  inter- 
pretation is  based.  It  will  appear  presently  that  there  is  also  an 
important  body  of  clinical  evidence  that  gives  support  to  the  view 
above  presented. 


SECTION  II 
THE  ORIGIN  OF  CANCER 

What  I  have  to  suggest  as  to  the  origin  of  cancer  follows  as  a 
matter  of  course  from  the  theory  just  outlined  as  to  the  nature 
of  the  disease. 

Whatever  tends  to  disturb  protein  metabolism  in  the  body  may 
be  considered  as  a  predisposing  cause  of  the  malady.  Familiar 
causes  of  such  disturbance  are  (1)  lack  of  exercise,  (2)  excess 
of  protein  food,  particularly  of  animal  proteins,  (3)  inadequacy 
of  the  protein  intake. 

It  is  obvious  that  the  second  and  third  of  these  causes  of  pro- 
tein maladjustments  are  mutually  exclusive.  They  must  both 
be  borne  in  mind.  An  excess  of  proteins  in  the  diet,  resulting 
in  a  putrefactive  mass  in  the  bowels  and  the  entrance  of  a  cer- 
tain amount  of  unbroken  protein  into  the  parenteral  system  may 
overwhelm  the  blood  corpuscles  and  produce  an  anaemic  condi- 
tion comparable  to  that  due  to  a  lack  of  adequate  protein  for  the 
building  up  of  fresh  supplies  of  blood  corpuscles. 

It  will  be  recalled,  of  course,  that  there  is  constant  destruction 
of  the  red  corpuscles  in  the  spleen  and  liver,  through  which 


226  THE  PROTEAL  TREATMENT  OF  CANCER 

(according  to  the  proteomorphic  theory)  byproducts  of  protein 
metabolism  that  are  toxic  in  character  are  excluded  from  the 
system.  To  compensate  this  destruction,  there  must  be  a  constant 
building  of  new  corpuscles,  implying  fresh  protein  supplies  and 
an  enormous  aggregate  expenditure  of  energy.  If  the  necessary 
protein  supplies  are  brought  in  excessive  quantities,  it  follows  that 
the  red  corpuscles  have  an  excess  of  byproducts  (of  the  poly- 
peptid  order)  to  deal  with  and  are  necessarily  destroyed  in 
excessive  numbers.  To  keep  up  the  supply,  calls  for  an  increased 
expenditure  of  energy,  putting  a  needless  tax  on  the  bodily  ma- 
chine that  may  manifest  itself  in  an  abnormal  blood  count, 
increased  blood  pressure,  and  ultimately  in  one  or  another  of  the 
conditions  of  localized  maladjustment  above  listed. 

But  it  does  not  by  any  manner  of  means  follow  that  the  only 
cause  that  can  produce  such  maladjustments  is  an  excess  of  pro- 
tein in  the  digestive  tracts.  It  has  already  been  implied  that  a 
marked  deficiency  might  lead  to  a  corresponding  sequence  of 
events.  The  presence  of  large  numbers  of  bacteria  in  the  intes- 
tinal tract  is  in  itself  a  factor  that  makes  constant  work  for  the 
red  blood  corpuscles,  resulting  in  a  steady  nitrogen  loss  and 
necessitating  a  constant  restocking  with  nutritive  proteins.  So 
protein  starvation  might  be  quite  as  disastrous  as  protein  reple- 
tion. The  happy  mean,  here  as  elsewhere,  constitutes  the  road 
to  health. 

As  to  exercise,  a  somewhat  similar  line  of  reasoning  applies. 
Every  physician  nowadays  recognizes  the  necessity  for  a  certain 
amount  of  exercise  in  normalizing  the  processes  of  metabolism. 
But  it  must  not  be  overlooked  that  excessive  exercise,  carried  to 
the  point  of  exhaustion,  may  have  a  devitalizing  influence  that 
will  lead  to  conditions  closely  comparable  to  those  resulting  from 
entire  lack  of  exercise.  Doubtless  a  hundred  persons  suffer  from 
lack  of  exercise,  however,  where  one  suffers  from  over  exercise. 
So  the  practical  lesson  that  one  is  commonly  called  upon  to 
inculcate  is  that  exercise  is  the  road  to  health. 

Vigorous  exercise  is  a  recognized  factor  stimulating  formation 
of  blood  corpuscles ;  which  fact,  according  to  the  present  theories, 
suggests  a  fairly  direct  association  between  exercise  and  preven- 
tion of  the  disturbances  of  protein  metabolism  that  are  here 
postulated  as  constituting  the  true  cancerous  condition. 

Whereas  lack  of  exercise  and  improper  diet  are,  in  my  opinion, 
the  chief  causes  that  lead  to  the  maladjustments  of  metabolism 
constituting  the  cancerous  condition,  there  are,  as  a  matter  of 
course,  many  minor  causes  of  disturbance.  Conspicuous  among 
these  is  the  loss  of  blood  which  many  women  suffer  at  the  meno- 
pause ;  a  condition  that  no  doubt  contributes  very  markedly  to  the 
genesis  of  malignant  neoplasms;  a  condition,  therefore,  which 


THE  ORIGIN  OF  CANCER  227 

should  always  receive  careful  attention  from  the  physician.  Any 
condition  that  causes  persistent  anaemia  should  be  viewed  with 
solicitude  in  this  connection. 

A  greater  or  less  degree  of  instability  conditioned  on  heredity, 
is  implied  as  a  matter  of  course,  as  determining  a  "tendency"  to 
cancer.  Hormone  disturbance  (e.  g.,  thyroid  inefficiency)  may 
also  constitute  a  predisposing  element. 

As  to  causes  that  determine  the  localized  development  of  a 
neoplasm,  when  the  cancerous  condition  eventuates  in  such 
development,  elaborate  studies  have  been  made,  and  there  is  vir- 
tual unanimity  of  opinion  among  authorities.  Any  chronic  source 
of  irritation  may  result — and  indeed  must  result — in  stimulus  to 
growth  of  new  cells.  A  callous  on  the  thumb  and  a  corn  on  the 
toe  illustrate  this  principle  as  tangibly  as  an  epithelioma  on  the 
lip  where  a  clay  pipe  has  long  been  held,  or  a  carcinoma  of  the 
breast  that  developed  from  a  nipple  irritated  by  a  corset  steel. 
But  the  thumb  callous  and  the  corn  are  "benignant"  growths 
because  their  tissues  are  not  of  a  character  to  be  broken  down 
by  the  bodily  enzymes.  The  same  is  true  of  an  ordinary 
overgrowth  of  fibrous  tissue  in  the  interior  of  the  body,  as  a 
fibroid  of  the  uterus  or  a  fibroma  located,  for  example,  on  the 
forearm. 

The  new  growth,  let  it  be  emphasized,  becomes  malignant  only 
when  its  character  is  such  that  its  cells  can  to  some  extent  be 
hydrolyzed  by  the  bodily  enzymes  (including,  prominently,  ac- 
cording to  present  thesis,  the  enzymes  of  the  white  and  red  cor- 
puscles). Moreover,  even  cells  falling  within  this  definition  are 
not  necessarily  a  menace  to  the  system,  provided  the  supply  of 
enzyme- forming  corpuscles  is  adequate  and  in  good  working 
order ;  for  in  that  case  misplaced  new  cells  are  at  once  dissociated 
and  the  products  of  such  dissociation  utilized  as  animo-acids  or 
eliminated  from  the  body.  According  to  the  proteomorphic 
theory,  the  early  stages  of  such  dissociation  are  effected  by  the 
white  corpuscles,  and  the  later  (polypeptid)  stages  by  the  red 
corpuscles ;  but  details  as  to  this  are  not  essential  to  the  present 
thesis.  What  is  essential  is  the  recognition  that  if  the  enzymes 
that  are  competent  to  hydrolyze  cells,  whenever  these  cells  are 
present  in  excess,  are  normally  abundant  in  the  system,  there  will 
be  no  development  of  a  malignant  neoplasm. 

Stated  otherwise,  the  presence  of  the  tangible  "malignant" 
neoplasm  is  in  itself  evidence  that  there  was  antecedent  disturb- 
ance of  the  processes  of  protein  metabolism  in  the  body,  charac- 
terized specifically  by  inadequacy  of  the  enzymes  that  deal  with 
proteins  not  needed  by  the  system. 

Viewed  from  a  slightly  different  angle,  it  appears  that  any 
proliferation  of  new  cells,  however  induced  e.g.,  in  repair  of  an 


228  THE  PROTEAL  TREATMENT  OF  CANCER 

ordinary  traumatism — is  a  potential  malignant  neoplasm;  the 
question  as  to  whether  it  becomes  an  actual  menace  being  deter- 
mined solely  by  the  antecedent  conditions  of  bodily  metabolism. 
As  illustrating  the  truth  of  this,  it  is  familiarly  known  that  normal 
blood  antagonizes  cancer  cells  when  introduced  from  without,  as 
in  the  case  of  an  inoculation  experiment  in  animals.  It  is  known, 
too,  that  transplantation  experiments  are  facilitated  by  bleeding 
the  animal  in  advance  of  transplantation. 

Summarizing  the  matter,  we  may  say  that  three  factors  are 
always  present  and  in  cooperation  when  a  malignant  neoplasm 
develops  in  the  human  subject.  There  is  (1)  the  factor  of  dis- 
turbed protein  metabolism,  which  I  have  spoken  of  as  the  can- 
cerous conditions;  there  is  (2)  the  factor  of  local  irritation, — a 
pipe  stem  on  the  lip,  an  injury  to  the  breast,  hot  food  in  the 
mouth  or  stomach,  chronic  intestinal  irritation,  a  laceration  of  the 
cervix  uteri;  and  there  is  (3)  the  factor  of  inherent  suscepti- 
bility, hereditary  or  acquired. 

It  is  the  old  story  of  stress  and  resistence.  The  same  irrita- 
tion being  applied  in  the  same  place  in  the  case  of  two  individuals, 
one  individual  suffers  no  obvious  inconvenience,  because  his 
defensive  mechanism  is  in  good  working  order;  and  the  other 
individual  develops  a  fatal  "cancer"  because  his  defensive  mech- 
anism is  not  in  effective  fighting  condition. 

This  view  harmonizes  the  contentions  of  those  theorists  who 
have  on  one  hand  alleged  the  general  origin  and  on  the  other, 
the  local  origin  of  cancer.  In  a  sense  both  theorists  are  right, 
inasmuch  as  there  would  probably  never  be  a  local  neoplasm 
developed  in  any  individual  case,  unless  there  was  some  source 
of  irritation.  So  there  is  every  reason  why  careful  attention 
should  be  paid  to  sources  of  local  irritation,  and  to  local  injuries 
of  every  character.  But  it  is  sheer  folly,  while  treating  these 
local  conditions,  to  ignore  the  underlying  systemic  maladjust- 
ments, correction  of  which  (where  this  is  possible)  would  make 
the  danger  from  local  irritation  negligible. 

In  other  words,  in  the  pro  founder  view,  the  problem  of  the 
origin,  and  therefore  the  problem  of  the  prevention,  of  cancer 
implies  attention  to  the  bodily  processes  of  metabolism — diges- 
tion, assimilation,  nutrition.  Mere  attention  to  local  conditions 
partakes  of  the  character  of  what  Thoreau  called  clipping  at  the 
twigs  of  the  tree  of  evil  while  the  roots  remain  untouched.  The 
root  of  the  cancerous  condition  is  disturbed  protein  metabolism, 
and  not  mere  local  irritation. 

I  shall  have  occasion  to  point  out  rather  obvious  corollaries  of 
this  view  in  their  application  to  the  question  of  the  surgical  treat- 
ment of  cancer,  as  well  as  to  make  what  I  hope  may  be  consid- 
ered important  deductions  as  to  more  effective  general  treatment 
of  the  malady. 


LOCAL  TREATMENT  OF   MALIGNANT   NEOPLASMS  229 

SECTION  III 

THE  LOCAL  AND  SURGICAL  TREATMENT  OF 
MALIGNANT  NEOPLASMS 

We  have  seen  that  the  development  of  a  local  neoplasm  implies 
defective  conditions  of  general  blood  supply. 

Such  deficiencies  may  be  accentuated  by  local  perversion  of 
circulation,  as,  for  example,  where  the  capillaries  and  veins  are 
rendered  patulous  by  the  persistent  application  of  heat,  as  in  the 
use  of  a  clay  pipe,  or  of  the  abdominal  heaters  carried  by  certain 
natives  of  the  Orient. 

In  a  slightly  different  way,  the  presence  of  an  excess  of  adipose 
tissue,  may  interfere  with  the  circulation,  and  tend  to  produce  a 
local  anaemia  even  while  the  general  blood  supply  is  fairly 
adequate. 

In  a  case  in  which  the  general  conditions  of  protein  metabolism 
were  just  at  the  border  line,  so  to  speak,  of  the  cancerous  condi- 
tion,— that  is  to  say,  of  out-and-out  abnormality, — a  compara- 
tively slight  interference  with  circulation  at  some  local  point  may 
give  opportunity  for  the  development  of  a  neoplasm  that  other- 
wise would  be  held  in  check. 

Such  a  condition  is  found,  for  example,  in  nearly  all  scar  tis- 
sue. Every  pathologist  knows  that  scar  tissue  is  poorly  supplied 
with  blood  vessels,  and  that  it  tends  rather  readily  to  break  down 
under  irritation.  In  other  words,  it  has  not  a  normal  degree  of 
resistance.  Doubtless  this  lack  of  resistance  is  closely  associated 
with  the  defective  blood  supply.  If,  now,  in  addition,  there  is 
some  source  of  irritation  that  tends  to  stimulate  the  growth  of 
the  cells  (as  all  irritation  does  tend  to  do),  conditions  are  favor- 
able for  the  development  of  a  neoplasm,  which  will  be  non- 
malignant  or  malignant  according  to  the  general  condition  of  the 
blood,  or  according  to  the  precise  character  of  the  new  tissue 
itself. 

If  the  balance  of  leucocytes  is  right,  and  there  is  an  adequate 
supply  of  red  corpuscles  to  deal  with  the  later  products  of  protein 
decompounding,  the  new  tissue  will  be  cared  for  by  the  system, 
and  the  condition  of  malignancy  cannot  develop. 

If,  on  the  other  hand,  the  red  cells  are  inadequate  either  in 
number  or  in  activity,  the  development  of  the  new  cells  will 
almost  of  necessity  result  in  a  condition  of  malignancy. 

Even  when  at  the  outset  the  red  cells  are  adequate  the  growth 
of  the  new  tissue  may  be  so  rapid  as  to  supply  a  larger  amount 
of  protein  than  can  be  dealt  with  (particularly  if  the  red  cells 


230  THE  PROTEAL  TREATMENT  OF  CANCER 

are  over-burdened  by  an  excess  protein  diet),  and  a  condition  that 
at  first  was  non-malignant  will  gradually  grade  into  malignancy. 

Such  a  change  from  a  benign  to  a  malignant  condition  is  a  mat- 
ter of  common  observation.  As  an  illustration,  note  how  ulcer 
of  the  stomach  tends  to  develop  into  cancer  of  the  stomach.  The 
presence  of  the  ulcer  tends  in  itself  to  interfere  with  digestion  and 
assimilation,  and  thus  to  superinduce  the  systemic  maladjustment, 
as  regards  protein  metabolism,  which  I  have  all  along  spoken  of 
as  the  cancerous  condition.  In  this  case,  the  initial  cause  of  the 
entire  difficulty  may  have  been  the  ingestion  of  a  morsel  of  hot 
food.  The  local  abnormality  here  precedes  the  systemic  one ;  but 
it  should  be  recalled  that  in  such  a  case,  if  the  person  swallowing 
the  hot  morsel  of  food  was  in  normal  health,  the  original  stomach 
lesion  was  an  ulcer  of  "benign"  character,  and  its  ultimate  malig- 
nancy was  sequential  to  the  general  condition  of  protein  malad- 
justment, as  in  the  case  of  every  other  malignant  neoplasm. 

Cancer  of  the  stomach,  however,  is  a  case  apart,  complicated 
by  the  fact  that  the  stomach  is  the  channel  of  intake  of  foods  to 
nourish  the  body  in  general.  With  malignant  neoplasms  in  gen- 
eral, it  is  a  safe  presumption  that  there  are  usually  deficiencies  of 
local  circulation  to  supplement  the  defects  of  the  general  blood 
supply.  The  uterus  depleted  by  hemorrhage  is  an  illustration 
in  point. 

It  follows  that  anything  which  tends  to  facilitate  the  circula- 
tion of  the  blood  in  and  about  the  malignant  neoplasm  may  be  of 
remedial  value,  provided  that  the  enzymic  conditions  of  the  blood 
have  not  shrunk  to  too  low  a  level. 

So  we  find  that  a  local  inflammation  may  sometimes  have  cura- 
tive effects  at  the  early  stage  of  development  of  a  malignant 
neoplasm.  The  cardinal  symptoms  of  inflammation — pain,  red- 
ness, and  swelling — are  associated  with  an  engorgement  of  the 
blood  vessels,  and  thus  with  an  increased  local  capacity  to  deal 
with  the  protein  elements.  The  true  explanation  of  inflammtion 
has  probably  never  hitherto  been  available  as  clearly  as  the 
proteomorphic  theory  reveals  it.  Hitherto  no  one  has  understood 
just  why  there  should  be  an  accumulation  of  red  blood  corpuscles 
at  a  source  of  inflammation.  That  the  process  was  curative  or 
beneficial  for  the  individuals  could  be  taken  for  granted,  but  as  to 
just  what  the  nature  of  the  benefit  conferred  might  be,  has  hitherto 
been  only  inferential.  Now  that  the  province  of  the  red  cor- 
puscles in  dealing  with  the  end-products  of  protein  metabolism 
is  understood,  the  benefits  of  the  inflammation  induced,  for 
example,  by  bacterial  onslaught  are  clearly  explicable.  The 
province  of  the  red  blood  corpuscle  is  to  cooperate  with  the  white 
corpuscles  by  carrying  away  and  further  proteolyzing  the  later 
products  of  protein  decompounding. 


LOCAL  TREATMENT  OF   MALIGNANT   NEOPLASMS  231 

Where  the  protein  in  question  is  new  tissue  of  cancerous  char- 
acter, the  process  of  decompounding  and  elimination  is  of  course 
entirely  comparable.  The  leucocytes  (in  particular,  probably, 
the  large  mononuclears)  begin  the  process  of  hydrolysis,  and  the 
red  corpuscles  continue  it  beyond  the  polypeptid  stage  and  carry 
away  the  toxic  by-products. 

So  we  might  expect  a  certain  amount  of  relief,  and  even  in 
favorable  cases  an  actual  curative  process,  to  be  engendered  by 
local  inflammation,  however  induced,  in  the  region  of  a  malignant 
neoplasm  at  an  early  stage.  Such  an  expectation  is  occasionally 
justified.  I  have  recently  had  called  to  my  attention  at  first  hand 
a  case  in  which,  seemingly,  an  accidental  streptococcus  infec- 
tion resulted  in  the  disappearance  of  an  epithelioma  of  the  lip 
quite  without  treatment;  and  this  observation  is  by  no  means 
unprecedented.  Doubtless  there  are  scores  of  irritative  or  caustic 
compounds  that  have  in  exceptional  instances  produced  the  "cure" 
of  a  local  epithelioma,  or  of  a  carcinomatous  ulcer  of  the  breast, 
through  inducing  such  a  local  inflammation. 

Such  cases,  however,  would  obviously  be  exceptional,  and  in 
general  it  is  to  be  hoped  that  a  local  inflammation  will  prove 
curative  in  any  case  of  a  well-developed  malignant  neoplasm  only 
in  occasional  instances.  As  an  adjunct  to  general  treatment,  how- 
ever, the  application  of  a  local  irritant  may  be  of  value.  But  at 
best  this  treatment  must  be  considered  as  an  adjunct  only. 

It  is  my  belief  that  much  the  same  statement  may  be  made 
with  regard  to  the  efficacy  of  the  treatment  of  the  local  neoplasm 
with  the  knife.  I  am  aware  that  this  view  is  heretical,  but  it 
follows  as  a  natural  conclusion  from  the  line  of  reasoning  above 
outlined. 

To  be  sure,  it  is  current  surgical  doctrine  that  if  cancer  can  be 
removed  early  enough,  and  removed  in  its  entirety,  the  patient 
is  cured. 

But  in  point  of  fact,  if  the  present  thesis  as  to  the  nature  of 
cancer  is  tenable,  the  surgeon  who  has  removed  a  malignant 
neoplasm, — even  in  its  earlier  stages,  and  even  though  the  removal 
had  been  as  complete  as  is  ever  feasible, — far  from  curing  the 
malady,  has  not  really  treated  the  malady  at  all.  He  has  removed 
a  local  manifestation  of  the  essential  systemic  abnormality  that 
is  the  true  "malignant  condition,"  but  at  best  the  treatment  is  a 
tentative  dealing  with  symptoms,  and  has  no  reference  to  the 
essential  disease  itself. 

It  is  true  that  the  removal  of  the  local  neoplasm  takes  away  a 
certain  amount  of  tissue  that,  through  partial  dissolution,  is 
poisoning  the  system ;  and  thus  may  be  a  valuable  aid  in  the  treat- 
ment of  the  amaladjustment  in  the  process  of  nutrition,  which 
constitutes  the  essential  character  of  cancer.  But  to  treat  the 


232  THE  PROTEAL  TREATMENT  OF   CANCER 

local  condition,  and  imagine  that  in  so  doing  one  has  cured  the 
malady,  is  hardly  less  futile  than  would  be  the  supposition  that 
one  has  cured  a  case  of  syphilis  because  one  has  excised  a  syphili- 
tic wart  or  healed  a  chancre  or  a  tertiary  ulcer  by  local  cauteriza- 
tion. 

The  futility  of  even  the  most  drastic  surgical  interference  is 
unequivocally  illustrated  by  the  history  of  a  case  examined  and 
diagnosed  by  me  in  which  both  breasts  and  the  axillary  glands  had 
been  removed  because  of  the  presence  of  small  nodules  which  were 
pronounced  of  doubtful  malignancy  by  a  competent  microscopist ; 
yet  in  which  the  blood  six  months  later  recorded  17  per  cent,  of 
large  mononuclear  leucocytes,  half  of  them  myelocytes,  leucoblasts, 
and  lymphoidocytes ;  together  with  red  cells  showing  poikilocytosis 
and  polychromasia,  and  not  infrequent  normoblasts,  evidencing  a 
condition  of  myelogenous  excitation  that — in  connection  with  the 
history  of  the  case — left  one  not  at  all  in  doubt  as  to  the  existence 
of  the  cancerous  condition.  Here  surgery  had  been  given  the  best 
possible  chance,  and  had  obviously  failed.  The  patient  died,  un- 
treated, six  months  later. 

It  does  not  follow  that  the  surgeon's  knife  should  be  held  in 
abeyance.  On  the  contrary,  there  is  the  most  logical  reason  for 
using  the  knife,  and  removing  as  much  as  possible  of  the  local 
neoplasm  that  evidences  the  systemic  disturbance.  But  such  a 
procedure  should  be  but  a  small  part  of  the  process  of  treatment 
of  the  cancerous  condition.  In  every  case  where  a  malignant 
neoplasm  is  removed  by  the  surgeon's  knife,  there  should  be  the 
most  careful  examination  of  the  blood,  with  full  count  of  the 
corpuscles  both  red  and  white,  and  differential  count  of  the  lat- 
ter. There  should  be  the  closest  scrutiny  of  the  patient's  habits 
of  living,  with  notable  reference  to  the  diet,  the  condition  of  the 
bowels  and  kidneys,  and  the  general  processes  of  assimilation  and 
bodily  metabolism.  Only  by  attention  to  these,  and  the  readjust- 
ment of  the  perturbed  process  of  assimilation,  can  there  by  any 
reasonable  grounds  for  hope  that  the  excised  neoplasm  will  not 
recur. 

It  is  partly  because  surgeons  usually  fail  to  give  such  attention, 
that  the  neoplasm  does  return  after  surgical  removal  in  so  pre- 
ponderant a  proportion  of  cases.  That  it  ever  fails  to  recur  must 
be  ascribed  to  the  good  luck  of  the  patient,  or  to  his  chance  obser- 
vation by  an  internist  of  discrimination  and  judgment,  rather 
than  to  any  merit  of  the  average  performer  of  the  operation. 

I  shall  have  something  more  to  say  presently  about  the  pre- 
operative  and  post-operative  treatment  of  malignant  neoplasms, 
suggesting,  among  other  things,  that  any  surgeon  who  fails  to 
avail  himself  of  therapeutic  measures  now  available  for  general 
treatment  of  the  case  in  connection  with  his  operations  must  be 


BIOLOGICAL  MEASURES  IN  THE  TREATMENT  OF  CANCER     233 

judged  guilty  of  gross  negligence,  amounting  to  malpractice.  But 
this  presentation  of  the  case  may  advantageously  be  delayed  until 
discussion  has  been  had  of  the  new  therapeutic  measures  in 
question. 


SECTION  IV 

"BIOLOGICAL  MEASURES"  IN  THE  TREATMENT 
OF  CANCER 

As  preliminary  to  such  discussion,  it  will  be  well  to  take  a  brief 
survey  of  various  tentatives  in  the  direction  of  the  general  treat- 
ment of  cancer,  made  in  recent  years,  that  have  seemed  to  have 
scientific  foundation  and  to  meet  with  a  certain  measure  of  suc- 
cess in  a  limited  number  of  cases ;  to  the  end  that  we  may  inquire 
whether  there  is  a  point  of  contact  between  these  different  kinds 
of  treatment. 

The  discovery  of  such  a  point  of  contact  would  obviously  give 
interesting  clues  to  the  further  investigation  of  the  subject. 

The  very  brief  examination  necessary  in  the  present  connec- 
tion may  advantageously  be  conducted  along  the  lines  of  the 
classification  or  synopsis  given  by  Bainbridge,  who  summarizes 
what  he  refers  to  as  "biological  measures"  for  the  cancer  treat- 
ment under  the  following  headings:  (1)  Bacterial  toxins,  (2) 
Antitoxic  sera,  (3)  Antitoxins,  (4)  "Toxins"  or  "Fluids,"  (5) 
Vaccines,  (6)  Residues,  Extracts,  and  Emulsions,  (7)  Serous 
Exudates  (Sera),  (8)  Opotherapeutic  measures. 

Among  the  examples  of  antitoxin,  antitoxic  sera,  and  bacterial 
toxins,  the  following  are  named:  (1)  Blastomycetic  antitoxic 
serum  of  Sanfelice,  based  upon  the  theory  that  cancer  is  due  to 
blastomycetes ;  (2)  Wlaeff's  Serum,  made  from  cultures  of 
blastomycetes  from  cancerous  inoculated  into  pigeons;  (3) 
Serum  of  Emmerich  and  Scholl,  made  by  inoculating  sheep  with 
Streptococcus  erysipelatosus;  (4)  Doyen's  Serum,  from  Micro- 
coccus  neoformans;  (5)  Schmidt's  Serum,  from  Mucor  muccdo 
(Cancroidin,  Antimeristem)  ;  (6)  Wyeth's  Toxins  of  Strepto- 
coccus; (7)  Coley's  Fluid — Mixed  toxins  of  Streptococcus 
erysipelatosus  and  Bacillus  prodigiosus. 

Among  the  vaccines  named  are  the  Mlcrococcus  Neoformans 
Vaccine  (Doyen),  used  in  connection  with  the  serum  made  from 
the  same  organism,  and  the  Bacterial  Vaccine  of  Jacob  and  Geets, 
made  from  cultures  of  the  same  micrococcus  sterilized  and 
standardized  according  to  the  opsonic  theory. 


234  THE  PROTEAL  TREATMENT  OF  CANCER 

Residues,  Extracts,  and  Emulsions,  include  Coca-Gilman  Ex- 
tract, or  Emulsion;  Vaughan  Residue;  the  Fichera  Emulsion, 
and  Autolyzed  Cancer  or  Normal  Tissue. 

Of  serous  exudates  and  body  fluids  there  is  a  long  list,  includ- 
ing Hodenpyl's  Ascitic  Fluid  from  a  cancer  subject;  Normal 
human  Blood  Serum;  blood  serum  of  the  horse  and  donkey; 
Hydrocele  Fluid;  Spermatocele  Fluid;  Ascitic  Fluid  from  the 
subject  of  alcoholic  cirrhosis;  Ascitic  Fluid  from  the  subject  of 
cardiac  insufficiency ;  and  Pleuritic  transudate  resulting  from 
broken  compensation. 

Of  Opotherapeutic  Measures  (organotherapy)  the  examples 
include  (1)  "Antituman"  of  Oestriech  made  from  embryological 
cartilage  and  arteries  from  which  a  supposedly  immunizing  sub- 
stance chondroitin-sulphate  is  extracted;  (2)  Thymus  Gland 
Extract;  (3)  Extract  of  Sheeps'  Thyroids;  and  (4)  Pancreatic 
enzymes,  Trypsin  and  Amylopsin  as  widely  exploited  a  few  years 
ago  under  the  auspices  of  Beard. 

As  to  the  status  of  these  various  treatments,  perhaps  I  cannot 
do  better  than  to  quote  Bainbridge's  summary  to  the  effect  that : 
"Many  of  the  agents  have  been  discarded,  with  practically  a  con- 
sensus of  opinion  against  their  efficacy ;  others  continue  to  receive 
a  certain  amount  of  attention,  largely  because  no  definite  test  of 
their  value  has  been  made  upon  a  convincing  basis;  while  still 
others  are  being  given  careful  consideration  by  a  sufficient  num- 
ber of  skilled  clinicians  to  warrant  the  hope  that  a  decision,  pro 
or  con,  will  be  soon  forthcoming." 

I  would  add,  however,  that  there  is  a  considerable  body  of 
evidence  to  show  that  a  good  many  of  these  diverse  agents  have 
seemed  to  produce  beneficial  effects  in  a  certain  number  of  cases, 
and  that  several  of  them  are  still  actively  employed  and  enthusi- 
astically championed  by  a  number  of  physicians.  Note,  for 
example,  the  report  of  Klinger  in  the  Correspondenz-Blatt  fur 
Schiveizer  Aerzte  for  Sept.  23,  1916,  on  the  results  obtained 
with  autolysates,  to  which  fuller  reference  will  be  made  in  another 
connection.  That  no  one  of  them  fully  meets  the  hopes  and 
expectations  of  its  originators  may,  doubtless,  be  accepted  as 
fairly  demonstrated.  But  I  think  it  must  also  be  clear  that  even 
tentative  results  would  hardly  have  been  attained  with  so  great 
a  variety  of  animal  extracts  unless  some  general  principle  was 
involved  that  gave  the  different  treatments  affinity. 

It  is  my  belief  that  the  principle  in  question  is  the  presence  of 
animal  or  bacterial  proteins  in  all  of  the  various  compounds  in 
question.  In  the  case  of  Beard's  Pancreatic  Enzymes  there  are 
also  present  digestive  ferments  closely  comparable  to  those  known 
to  be  evolved  by  the  white  blood  corpuscles,  the  manner  of  action 
of  which  will  be  dealt  with  presently. 


BIOLOGICAL  MEASURES  IN  THE  TREATMENT  OF  CANCER      235 

For  the  moment,  the  point  that  I  would  emphasize  is  that  the 
entire  group  of  biological  cancer  remedies  as  above  outlined  com- 
prises agents  of  very  diversified  origins  that  have  at  least  one 
prominent  point  of  contact  in  the  presence  of  organic  proteins. 

If  we  add  that  among  all  the  numberless  agents  that  have  been 
used  in  the  general  treatment  of  cancer,  there  is  not  one  at  present 
commanding  the  slightest  scientific  consideration  that  does  not 
contain  protein,  we  are  at  least  put  in  the  way  of  an  interesting 
and  suggestive  line  of  thought. 

The  ideas  thus  engendered  are  naturally  linked  with  the  reflec- 
tion that  many  students  of  cancer  have  attempted  to  associate 
the  genesis  of  the  disease  with  defects  of  protein  assimilation; 
and  also  with  the  very  interesting  studies  of  Bulkley  in  the  treat- 
ment of  cancer  by  careful  regulation  of  the  diet  with  reference 
to  the  protein  intake. 

The  full  bearing  of  the  observation,  however,  is  appreciable 
only  when  we  reflect  along  the  line  of  the  now  familiar  physio- 
logical principle  that  the  introduction  of  a  foreign  protein  paren- 
terally  leads  to  a  development  by  the  body  of  antibodies  to 
antagonize  the  toxic  influence  of  that  protein;  and  the  further 
reflection  that  the  antibodies  in  question  are  produced  by  the 
system  in  excess  of  the  quantity  required  merely  to  neutralize 
the  foreign  agent. 

A  classical  illustration  of  this  is  found  in  the  use  of  the  anti- 
typhoid vaccine,  which  leads  to  the  production  of  antibodies  in 
such  excess  as  to  give  the  individual  immunity  to  the  typhoid 
virus  for  a  term  of  months  or  years. 

A  moment's  further  reflection  shows  that  the  antibodies  thus 
produced  when  a  foreign  protein  is  introduced  in  the  body  must 
be  of  a  character  to  effect  the  decompounding  of  the  protein 
molecule.  If  the  thesis  of  the  Proteomorphic  theory  is  accepted, 
it  follows  that  the  introduction  of  a  foreign  protein  will  result 
in  the  increased  activities  of  the  white  and  red  blood  corpuscles 
and  of  the  organs  that  produce  these  corpuscles.  Specifically,  we 
may  expect  that  after  introduction  of  a  foreign  protein  there 
will  be  observable  a  modification  of  the  blood  count  in  the 
direction  of  an  increase  of  large  mononuclear  lymphocytes  and 
red  blood  corpuscles.  We  may  assume  that  there  is  a  responsive 
increase  in  the  quantitative  enzymic  activities  of  these  corpuscles, 
and  that  the  aggregate  effect  exceeds  the  immediate  needs  of  the 
system  as  induced  by  the  invading  protein. 

In  other  words,  there  will  remain  a  residual  quantity  of  en- 
zymes in  the  blood  capable  of  decompounding  proteins. 

These  residual  enzymes  obviously  constitute  an  agent  capable 
of  attacking  other  foreign  proteins,  unless  we  assume  that  they 


236  THE  PROTEAL  TREATMENT  OF  CANCER 

are  of  so  specific  a  character  that  they  can  affect  only  the  par- 
ticular protein  that  has  invoked  them. 

Have  they  such  specificity? 

This,  obviously,  is  an  important  question.  But  I  think  there 
can  be  no  doubt  about  the  answer.  The  enzymes  that  begin  the 
decompounding  of  the  protein  molecule  are  of  a  tryptic  character, 
closely  comparable  apparently  whether  secreted  by  the  digestive 
glands  or  by  the  white  corpuscles,  and  their  action  is  very  general. 
The  same  enzyme  can  affect  the  decompounding  of  animal  and 
vegetable  proteins  of  the  most  varied  character,  as  the  normal 
digestion  of  an  ordinary  meal  in  the  intestinal  tract  sufficiently 
demonstrates.  Moreover,  it  is  specifically  observed  that  the  white 
blood  corpuscles  can  attack  and  destroy  bacterial  proteins  of 
many  types.  There  are  abundant  reasons  to  believe,  then,  that  the 
enzymes  developed  as  antibodies  to  any  one  of  the  wide  range  of 
foreign  proteins  introduced  parenterally  may  be  able  to  effect  the 
decompounding  of  other  proteins  than  the  particular  one  intro- 
duced. 

If,  now,  we  reflect  that  the  cells  of  a  malignant  neoplasm  are 
made  up  of  protein  which,  notwithstanding  its  close  general  simi- 
larity to  that  of  normal  tissues,  is  in  a  sense  a  foreign  protein; 
and,  moreover,  that  these  cells  because  of  their  newness  and  rapid 
growth  lack  something  of  the  stability  of  matured  normal  cells, 
it  is  readily  explicable  that  they  may  be  attacked  by  the  protein 
antibodies  in  the  blood  and  decompounded. 

As  suggesting  a  chemical  basis  for  the  expectation  that  an  agent 
might  be  developed  that  would  differentiate  between  normal  cells 
and  cancer  cells,  we  may  note  the  researches  tending  to  show 
that  cancer  cells  have  a  mineral  content  in  excess  of  the  normal; 
and,  specifically,  that  the  more  malignant  types  of  cancer  cells 
are  relatively  rich  in  potassium,  less  malignant  ones  showing  a 
relative  preponderance  of  calcium ;  also  the  fact,  to  be  dealt  with 
in  another  connection,  that  cancer  tissue  is  reported  as  showing 
only  70  per  cent,  of  the  nitrogen  content  of  normal  tissue. 

If  the  protein  antibodies  in  the  blood  come  in  sufficient  quanti- 
ties, it  is  even  conceivable  that  the  cells  of  the  neoplasm  may  be 
altogether  dissociated,  and  the  neoplasm  itself  thus  eliminated. 
But  of  course  so  radical  a  result  as  this  could  be  expected  only 
in  very  exceptional  cases  in  which  the  balance  between  the  normal 
activities  of  the  corpuscles  and  the  activities  of  the  cells  of  the 
neoplasm  had  not  been  too  profoundly  disturbed. 

This  is  perhaps  equivalent  to  saying  that  success  might  be 
expected  somewhat  in  proportion  to  the  stage  of  advancement  of 
the  cancerous  condition  in  general  and  of  the  neoplasm  in 
particular. 

A  highly  important  complication  is  found,  however,  in  the  fact 


BIOLOGICAL  MEASURES  IN  THE  TREATMENT  OF  CANCER     237 

that  the  animal  and  bacterial  foreign  proteins  now  under  discus- 
sion as  furnishing  the  agents  to  stimulate  the  corpuscular  en- 
zymes, are  in  themselves  more  or  less  toxic  bodies.  All  foreign 
serums  have  elements  of  toxicity,  and  this  may  be  so  pronounced 
that  the  aggregate  effect  of  introduction  of  the  foreign  proteins 
may  be  the  opposite  of  remedial.  As  a  case  in  point,  the  intro- 
duction of  a  foreign  blood  serum  may  cause  active  haemolysis, 
so  that  the  blood  count  goes  down  instead  of  up.  But  this,  prop- 
erly interpreted,  is  in  itself  an  evidence  of  such  activities  of  a 
foreign  protein  as  are  above  postulated,  the  destruction  of  the 
red  blood  corpuscles  evidencing  exactly  such  activities  in  connec- 
tion with  the  elimination  of  the  byproducts  of  hydrolosis  of  for- 
eign proteins  as  is  postulated  in  the  Proteomorphic  Theory. 

But  it  is  obvious  that  from  a  therapeutic  standpoint  the  relative 
toxicity  of  the  protein  introduced  is  of  paramount  importance. 
And  this  observation  furnishes  the  clue  to  a  comprehensive  criti- 
cism of  the  entire  list  of  biological  agents,  above  referred  to  as 
comprising  the  various  cancer  remedies.  The  bacterial  agents 
employed  in  making  the  various  serums  of  Emmerich  and  Wyeth 
and  Coley  are  confessedly  toxic;  and  the  various  and  sundry 
animal  serums  are  all  known  to  have  active  toxicity  when  intro- 
duced into  heterologous  parenteral  systems. 

Hence  in  practice  it  happens  that  in  using  any  of  these  various 
vaccines  and  serums  we  are  introducing  agents  capable,  to  some 
extent,  of  combating  the  cancer  cell  (indirectly),  but  also  agents 
that  put  a  severe  tax  on  the  enzyme- forming  organs  (blood  cor- 
puscles and  cytogenic  apparatus)  they  are  designed  to  aid.  In 
using  these  agents,  then,  there  is  always  danger  that  when  we 
take  one  step  up  the  hill  we  shall  slip  back  the  length  of  two 
steps.  In  other  words,  while  we  are  by  way  of  "curing"  the  can- 
cer, we  may  kill  the  patient. 

As  I  have  already  suggested,  it  is  only  in  a  small  residual  mini- 
mum of  cases  that  we  can  hope  to  find  the  balance  of  nutritional 
conditions  in  the  system  such  that,  when  by  a  happy  chance  we 
stumble  on  the  right  dosage  of  foreign  protein,  the  aggregate 
results  of  our  effort  is  beneficial,  and  the  local  neoplasm  is  caused 
to  regress. 

Nevertheless,  the  evidence  of  these  scattered  and  isolated  cases, 
in  the  midst  of  the  great  mass  of  failures,  is  in  the  highest  degree 
encouraging  and  enheartening,  because,  properly  interpreted,  it 
tends  to  establish  the  general  principle  that  the  use  of  foreign 
proteins  may  be  of  value  in  the  treatment  of  the  cancerous  con- 
dition. Even  though  the  entire  list  of  "biological  remedies" 
should  stand  condemned,  these  tentative  remedies  will  have  served 
a  useful  purpose  in  pointing  the  way  to  a  line  of  medication  which 
retains  their  advantages  and  eliminates  their  disadvantages. 


238 


THE   PROTEAL   TREATMENT   OF   CANCER 


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THE  EVOLUTION   OF  THE   PROTEIN   PRINCIPLE  239 

SECTION    V 
THE  EVOLUTION  OF  THE  PROTEIN  PRINCIPLE 

Charles  Darwin  was  accustomed  to  emphasize  the  value  of 
hypothesis  as  an  aid  to  scientific  discovery.  This  value  is,  indeed, 
so  evident  that  the  statement  of  it  is  almost  a  truism.  Yet  it  is 
equally  true  that  a  false  hypothesis  may  constitute  one  of  the  most 
hampering  of  obstacles  in  the  way  of  progress. 

I  was  forcibly  reminded  of  this,  when,  a  few  weeks  after  the 
issue  of  the  first  edition  of  the  Monograph  so  frequently  referred 
to,  I  came  upon  a  report  that  had  hitherto  escaped  my  attention, 
in  which  an  account  was  given  of  some  very  remarkable  experi- 
ments in  the  treatment  of  cancer  in  the  human  subject  with  an 
alleged  "X"  substance  said  to  be  extracted  from  thymus  of  the 
calf.  The  report  appears  in  a  volume  issued  by  Columbia  Uni- 
versity Press  in  the  year  1913  captioned  "Studies  In  Cancer  and 
Allied  Conditions,"  and  said  to  be  issued  from  the  department  of 
zoology,  surgery,  clinical  -pathology,  and  biological  chemistry 
under  the  auspices  of  the  George  Crocker  Special  Research  Fund 
at  Columbia  University. 

This  is  one  of  a  series  of  volumes  with  which  I  had  consider- 
able familiarity,  but  I  had  failed  to  note  the  essential  part  of  the 
particular  report  in  question;  otherwise  I  should  very  eagerly 
have  welcomed  it  as  giving  support  to  a  quite  different  theory 
from  the  one  that  the  authors  of  the  investigations  were  pursuing. 

The  report  in  question  bears  title  "The  Relation  of  Certain 
Internal  Secretions  to  Malignant  Tumors."  The  investigation 
was  said  to  be  conducted  "with  the  idea  of  throwing  some  light 
on  the  relation  of  some  of  the  internal  secretions  to  malignant 
tumors."  But  in  point  of  fact,  the  part  of  the  report  to  which 
I  refer  has,  in  my  opinion,  no  essential  relations  to  the  subject 
of  internal  secretions.  The  investigation  was  indeed  conducted 
with  the  aid  of  extracts  made  from  the  thymus  gland ;  but  in  my 
opinion  that  fact  was  merely  incidental,  and  precisely  the  same 
results  would  -have  been  attained  had  the  extracts  been  made  from 
any  one  of  a  score  of  other  tissues  of  the  animal  body. 

In  other  words,  in  my  opinion — and  indeed,  in  the  light  of  new 
evidence,  I  think  it  hardly  open  to  doubt — the  observations  made 
had  reference  to  the  results  of  introducing  foreign  proteins  into 
the  parenteral  system,  though  the  authors  themselves  make  it 
positively  clear  that  they  had  no  such  conception.  Probably  they 
will  repudiate  the  suggestion  now  that  it  is  made.  Nevertheless 
I  believe  the  suggestion  to  be  entirely  valid. 


240  THE   PROTEAL   TREATMENT   OF   CANCER 

The  results  achieved,  in  the  treatment  of  49  cases  of  inoperable 
cancer  in  the  human  subject,  were  so  striking  that  I  shall  have 
occasion  to  summarize  them  in  a  moment,  and  to  make  brief 
quotations  from  the  case  records.  I  shall  cite  also  results  attained 
by  Klinger  in  the  treatment  of  cancer  with  his  animal  autoly sates, 
for  comparison  with  the  results  attained  in  the  use  of  vegetable 
proteins.  It  will  be  clear,  I  think,  that  there  is  at  least  a  strong 
presumption — when  we  note  the  striking  similarity  of  these  inde- 
pendent reports  as  to  the  effect  on  the  pain  of  the  cancer  subject, 
on  the  character  of  the  discharge  from  the  tumor,  and  on  the 
tumor  itself — that  a  common  principle  is  involved  in  the  three 
types  of  therapeutic  procedure.  And  it -seems  to 'be  scarcely  open 
to  question  that  the  most  plausible  hypothesis — to  put  the  case 
mildly — as  to  the  character  of  this  common  agent  is  the  assump- 
tion that  it  is  a  protein  or  a  protein  derivative. 

Had  the  authors  of  the  paper  in  question  conceived  that  pro- 
teins were  indeed  the  active  agent  in  their  remedy,  their  entire 
outlook  on  the  subject  would  have  been  changed,  and  in  ev^ry 
probability  they  would  have  gone  forward  to  perfect  a  discovery 
at  the  verge  of  which  they  paused.  That  they  missed  the  dis- 
covery, yet  missed  it  narrowly,  is  revealed  almost  pathetically  in 
the  summary  of  conclusion  with  which  they  finished  their  paper, 
when,  following  deductions  that  are  not  pertinent  to  the  present 
aspect  of  the  subject,  they  conclude: 

"(3)  That  there  is  a  substance  common  to  many  tissues,  but 
present  in  varying  degrees,  which  has  a  positive  influence  in 
immunity  and  cure  in  animals. 

"(4)  That  the  application  of  these  results  to  the  treatment  of 
human  tumors  results  in  a  temporary  improvement  in  some  cases, 
and  in  some  few  cases  in  an  apparent  cure. 

"(5)  That  there  is  still  lacking  something  which  will  carry 
improvement  observed  to  a  successful  issue.  In  what  direction 
search  for  such  a  substance  or  for  an  explanation  of  the  problem 
is  to  be  made  is  at  present  unknown." 

The  concluding  sentence  makes  it  unqualifiedly  clear  that  the 
authors  were  entirely  at  sea ;  that  their  observations  were  merely 
empirical ;  and  that  they  came  to  no  generalizations  that  could  by 
any  possibility  be  claimed  as  constituting  the  discovery  of  the 
protein  principle.  Had  they  made  such  a  generalization,  the 
entire  history  of  the  cancer  problem  would  have  been  changed 
from  that  moment ;  and,  quite  incidentally,  my  own  work  in  this 
field  would  have  been  unnecessary  and  would  never  have  been 
undertaken. 

Looking  back,  in  the  light  of  recent  developments,  it  seems 
strange  that  the  authors  should  have  failed  of  the  prevision,  the 
imagination,  that  would  link  their  observations  one  with  another 


THE   EVOLUTION   OF  THE   PROTEIN   PRINCIPLE  241 

and  reveal  a  unifying  principle.  But  this  is  the  history  of  every 
discovery  in  science  when  viewed  in  retrospect.  The  reader  of 
my  History  of  Science  will  be  familiar  with  numberless  instances 
in  point.  He  will  recall  that  the  usual  difficulty  is  that  the 
imagination  is  hampered  by  preconceptions  of  the  experimenter 
based  on  a  false  hypothesis  of  one  type  or  another. 

In  the  present  instance,  the  hampering  hypothesis  was  the 
thought  that  the  "substance  common  to  many  tissues  .  .  . 
which  has  a  positive  influence  in  immunity  and  cure  in  animals," 
and  even  in  the  alleviation  of  pain  in  inoperable  cancer  in  the 
human  subject,  is  an  obscure  substance,  the  method  of  extraction 
of  which  was  supposed  to  be  known  only  to  a  single  individual — 
namely,  Dr.  Frederick  Gwyer,  of  New  York — and  which  was  of 
so  problematical  a  character  that  the  name  "X"  -substance  was 
given  to  it.  We  are  told  that  "the  chemistry  and  method  of 
isolation  of  this  active  substance  being  preeminently  the  field  of 
Dr.  Gwyer,  we  shall  not  speak  of  it."  So  it  appears  that  the 
experimenters  were  working  with  something  -which  they  regarded 
as  mysterious ;  of  which,  to  be  sure,  they  knew  the  general  origin, 
but  regarding  the  precise  methods  of  preparation  of  which  they 
were  altogether  in  the  dark. 

This  was  peculiarly  unfortunate,  both  because  it  savors  of  an 
unscientific  method  of  procedure,  and  because  the  secrecy  in  this 
case  probably  stood  in  the  way  of  progress ;  for  it  is  hardly  con- 
ceivable that,  had  the  method  of  extraction  employed  by  Dr. 
Gwyer  been  made  known  to  all  of  the  workers,  there  should  not 
have  been  some  one  of  them  who  would  have  fathomed  the  open 
secret, — devining,  what  the  originator  of  the  process  doubtless 
himself  altogether  failed  to  surmise,  that  the  "X-substance," 
interpreted  in  scientific  terms,  is  merely  protein,  or  a  product  of 
partial  protein  hydrolysis. 

But  the  minds  of  the  operators  were  under  sway  of  the  "X-sub- 
stance" hypothesis,  and  hence  they  were  not  in  the  least  en- 
lightened when  animal  tissues  various  and  sundry  were  subjected 
to  observation  "to  see  if  the  'X'-substance  is  widely  spread  in 
tissues  or  if  limited  to  the  thymus,"  and  were  informed  that  it 
could  be  found  in  a  great  variety  of  animal  tissues.  A  table  is 
given,  naively  showing  that  Dr.  Gwyer  has  extracted — by  a 
method  "not  yet  published" — varying  quantities  of  the  "X"  sub- 
stance from  macerated  human  embryo,  uterine  fibroid,  chronic 
cystic  masstitis  of  the  breast,  and  liver  of  chronic  congestion  in 
the  human  subject ;  from  muscle,  thyroid,  thymus,  testes,  spleen, 
pituitary,  adrenal,  and  ovary  of  beef  creature ;  from  carcinoma, 
heart,  stomach,  spleen,  kidney,  sarcoma,  lung,  liver,  intestines, 
and  testes  of  the  rat ;  and  from  fluid  from  a  carcinomatous  cyst, 


242  THE  PROTEAL  TREATMENT  OF  CANCER 

abdominal  ascitic  fluid  from  a  tumor,  and  from  carcinoma  in 
the  mouse. 

Furthermore  "Gwyer  next  examined  several  of  the  reported 
curative  agents  for  cancer  and  found  'X'  substance  in  all  those 
mentioned,  namely  (1)  Ascitic  fluid  from  a  case  of  stationary 
carcinoma  in  the  human;  (2)  calf  thymus;  (3)  sheep  thyroid; 
(4)  rat  carcinoma  tissues  prepared  after  Vaughn's  method; 
and  (5)  rat  carcinoma  tissues  prepared  after  the  method  of  Coca 
and  Gilman." 

Still  another  table  is  published  which  shows  "the  interesting 
fact  that  immune  animals  contain  more  of  this  'X'  substance  than 
non-immune."  It  appears  from  this  table  that  the  quantitative 
differences  in  question  are  very  slight,  the  range  of  variation 
being  given  as  .011  1/10  to  .014%  grms.  per  gram  of  dried  body 
weight;  and  we  are  given  no  analysis  of  methods  to  assure  us 
that  these  variations  do  not  lie  within  the  limits  of  experimental 
errors.  The  figures  serve,  nevertheless,  to  show  that  Gwyer's 
tests  were  apparently  not  applied  for  the  detection  of  the  full- 
sized  .protein  molecule  as  such,  but  to  some  derivative  product. 
The  fact  stands  out,  however,  and  from  the  present  standpoint 
is  all-essential,  that  all  the  experiments  in  question  deal  with 
tissues  or  substances  rich  in-  proteins.  This  of  course  does  not 
by  itself  establish  proteins,  as  such,  as  -the  active  agents  in  the 
remedial  process ;  but  it  does  raise  a  strong  presumption — taken 
in  connection  with  the  mass  of  new  evidence  presented  in  the 
present  book — that  either  the  protein  molecule  or  one  of  its 
derivative  products  in  the  form  of  proteoses,  peptones,  or  poly- 
peptids  is  the  active  principle  involved.  There  seems  no  present 
need  of  invoking  an  "X"  substance. 

Unfortunately,  however,  this  mysterious  substance  was  invoked, 
and  hence  the  physicians  who  administered  the  treatment  were, 
in  their  own  estimation,  performing  what  was  in  effect  a  mysteri- 
ous rite.  If  we  appluad  the  freedom  from  prejudice — altogether 
unusual  in  men  of  their  position — that  permitted  them  to  employ 
what  they  regarded  as  a  secret  agent,  of  unknown  method  of  prep- 
aration, in  the  treatment  of  a  human  malady,  we  must  at  the 
same  time  deprecate  their  unfortunate  thraldom  to  superstition 
in  focalizing  ^attention  on  the  supposed  mysterious  agent,  when 
there  was  every  warrant  for  a  simple  scientific  deduction  to  the 
effect  that  they  were  really  dealing  with  agents  familiar  to  every 
physiological  chemist. 

Be  that  as  it  may,  'however,  the  mistake  was  made,  and  so 
it  unfortunately  resulted  that,  notwithstanding  the  very  interest- 
ing and,  properly  interpreted,  important  results  achieved,  nothing 
of  permanency  or  real  significance  came  of  the  investigation.  It 
being  seen  that  the  magical  "X"  substance  did  not  ultimately  act 


THE   EVOLUTION    OF   THE   PROTEIN    PRINCIPLE  243 

with  necromatic  efficiency,  notwithstanding  its  early  promise,  the 
experimenters  seemingly  abandoned  it,  and,  standing  with  numer- 
ous other  agents  of  similar  potency  in  their  hands — had  they  but 
known  it — they  make  the  bewildered  declaration :  "That  there  is 
still  lacking  something  which  will  carry  the  improvement  observed 
to  a  successful  issue";  and,  almost  wilfully  shutting  their  eyes 
lest  the  truth  be  revealed  to  them,  they  add :  "In  what  direction 
search  for  such  a  substance  or  for  an  explanation  of  the  problem 
is  to  be  made  is  at  present  not  known." 

And  this  bewildered  confession  of  defeat  is  printed  on  a  page 
opposite  which  lies  a  table  telling  of  really  remarkable  results 
achieved  in  the  treatment  of  human  carcinomas  and  sarcomas, 
all  inoperable  and  supposedly  hopeless,  in  which  two  cases  were 
apparently  cured;  twenty-two  cases  "greatly  improved  for  a 
period" ;  five  cases  "slightly  improved  for  a  period" ;  and  only 
sixteen  cases  treated  without  effect.  This  table  summarizes  the 
text  in  which  we  are  told  explicitly  what  was  the  character  of  the 
improvement  noted.  Here  are  some  of  the  effects :  "The  tumor 
becomes  gradually  smaller,  softer,  and  in  some  cases  ulcerated, 
and  large  portions  may  be  sloughed  off.  In  those  cases  where 
there  has  been  a  large  amount  of  discharge,  notably  in  the  uterine 
cases,  this  discharge  has  markedly  decreased  and  in  some  cases 
stopped.  The  pain  is  relieved  to  a  most  remarkable  extent;  in 
one  case,  for  example,  where  morphine  was  given  in  doses  of  2 
grains  in  twenty-four  hours,  5  mms.  per  day  of  the  extract  were 
sufficient  to  enable  the  patient  to  do  without  the  morphine  until 
her  death  four  months  later.  Some  tumors  that  were  ulcerated 
on  beginning  treatment  after  slight  reduction  in  size  became 
covered  with  normal  epithelium." 

It  is  quite  true  that  the  report  continues  with  this  statement: 
"Unfortunately,  however,  aside  from  the  relief  of  pain,  these 
results  do  not  persist  in  all  of  the  cases.  The  improvement  noted 
goes  on  from  4  to  8  weeks  and  then  there  is  a  gradual  return  to 
the  old  conditions."  But  it  is  added :  "The  tumor,  however,  does 
not  grow  as  fast  as  would  be  expected  and  some  of  the  cases  have 
lived  longer  than  ordinary  clinical  experience  would  indicate  as 
the  expected  period  of  life."  Moreover,  detailed  case  histories 
are  given  of  a  recurrent  carcinoma  of  the  breast  in  which :  "The 
mass  grew  steadily  smaller  and  after  fifteen  injections  dis- 
appeared. There  has  been  no  recurrence  to  date,  which  is  sixteen 
months  after  treatment;  and  of  a  case  of  inoperable  carcinoma 
of  the  corpus  of  the  uterus  which  became  operable  under  treat- 
ment and  apparently  as  a  direct  result  of  the  treatment,  in  which 
the  patient  was  free  from  recurrence  twenty- four  months  after 
operation,  although  she  died  thirty  months  after  operation,  of  re- 
currence, the  thymus  injection  not  being  kept  up  after  operation." 


244  THE   PROTEAL   TREATMENT  OF   CANCER 

Viewing  such  results  in  retrospect,  and  recalling  that  a  positive 
statement  is  made:  "All  of  the  patients  treated,  49  in  number, 
have  been  declared  surgically  inoperable  and  the  growth  positively 
malignant,  both  clinically  and  microscopically,"  it  seems  almost 
incredible  that  the  record  of  such  results,  achieved  under  the 
auspices  of  a  great  university  and  published  with  the  authentica- 
tion of  an  important  bureau  for  cancer  research,  should  have 
aroused  no  interest  on  the  part  of  other  workers,  and  have  led 
to  no  practical  result  looking  toward  the  solution  of  the  cancer 
problem.  And  I  think  we  must  feel  that  the  barrenness  of  the 
effort  was  largely  due  to  the  unfortunate  hypothesis  with  which 
the  striking  results  were  linked  in  the  minds  of  the  experimenters 
and  in  the  minds  of  the  readers  of  their  report. 

Here  were  results  attained  with  an  alleged  "X"  substance  of 
mysterious  origin,  of  unknown  composition,  a  subtsance  that  no 
one  knew  how  to  duplicate — the  private  property,  as  it  were,  of 
the  physician  who  had  discovered  it.  Under  the  circumstances, 
other  searchers  in  the  cancer  field  probably  felt  that  they  could 
do  nothing  except  await  further  reports  from  the  alleged  dis- 
coverer himself;  and  as  these  reports  were  not  forthcoming, 
progress  in  that  direction  was  at  an  end.  It  seems  regrettable 
that  some  one  did  not  raise  the  query  as  to  whether  the  alleged 
mystery  of  the  "X"  substance  were  not  mythical,  and,  by  making 
similar  experiments  with  thymus  extract  prepared  in  a  non- 
mysterious  way,  following  these  up  with  other  extracts,  carry  the 
experiment  forward  a  step  farther  along  the  lines  of  conquest  of 
cancer. 

In  point  of  fact,  k  appears  that  at  least  one  experimenter  did 
do  this,  although  whether  he  knew  of  the  work  of  the  "X"  sub- 
stance experimenters  or  not  I  cannot  say.  I  refer  to  Klinger, 
the  Swiss  physician  whose  work  with  animal  autolysates  was 
referred  to  in  an  earlier  part  of  this  volume.  He,  in  effect,  did 
precisely  what  has  just  been  suggested.  He  tested  animal  extracts 
of  no  mysterious  character,  using  them  hypodermically  quite  as 
the  'Columbia  University  experimenters  had  used  the  "X"  sub- 
stance. Like  them  he  produced  striking  results  in  the  early  stage 
of  treatment  of  cases  of  inoperable  cancer.  Like  them  he  saw 
that  it  was  necessary  to  find  other  substances  which  "will  carry 
the  improvement  to  a  successful  issue."  But,  unlike  them,  he  did 
not  feel  that  "the  direction  of  search  for  such  a  substance  or  for 
an  explanation  of  the  problem  was  quite  unknown."  In  some 
way  he  divined  that  it  might  be  worth  while  to  test  other  animal 
extracts  after  the  efficiency  of  the  first  one  had  been  exhausted. 
In  so  doing  he  found  that  a  new  term  of  improvement  followed. 
Thus  he  was  one  stage  nearer  the  final  goal. 

And,  as  the  reader  is  aware,  at  the  same  time  that  this  ex- 


THE   EVOLUTION    OF   THE   PROTEIN    PRINCIPLE  245 

tension  of  methods  was  being  employed  by  Klinger  in  Switzer- 
land, my  associates  and  I  were  working  quite  independently  along 
precisely  similar  lines,  using  vegetable  proteins  for  the  most  part 
instead  of  animal  proteins,  with  strikingly  analogous  results. 

Klinger's  results  are  published  in  the  Korrespondenz-Blatt  fiir 
Schweizer  Aerzte,  September  23,  1916.  A  lengthy  summary  of 
the  article  appears  in  the  Journal  of  the  American  Medical  Asso- 
ciation for  November  4,  1916.  No  one  could  fail  to  note  the 
similarity  of  the  description  of  Klinger's  results  with  his  auto- 
lysates  to  my  previously  published  reports  of  results  obtained  with 
vegetable  proteins.  For  example,  he  says,  as  condensed  in  the 
Journal  of  the  American  Medical  Association: 

"Quite  a  number  of  cases  have  been  reported  of  complete  cures 
or  essential  improvement  under  Autolysate  treatment  of  previous- 
ly inoperable  cancer.  In  Betrand's  case  an  extensive  recurrence 
of  a  mammary  cancer  was  completely  cured.  On  suspension  of 
the  treatment  after  several  months  of  daily  injunction,  the  tumor 
began  to  grow  again.  The  resumption  of  growth  on  suspension 
of  the  treatment  apparently  shows  that  the  cure  was  not  a  spon- 
taneous subsidence  of  the  tumor  but  was  actually  the  work  of  the 
treatment.  Such  brilliant  results  are  exceptional.  But  even  in 
the  only  improved  cases  the  inflammatory  infiltration  may  sub- 
side and  the  tumor  may  cast  off  necrotic  masses,  the  edge  of  the 
ulceration  healing  over.  Cancers  bleeding  and  suppurating  pro- 
fusely may  have  the  bleeding  and  secretion  arrested.  The  tumor 
often  grows  so  much  smaller  that  the  esophagus  or  the  rectum 
may  become  permeable  once  more.  Pains  caused  by  the  infiltra- 
tion subside  as  this  retrogresses.  In  many  cases  the  growth  be- 
comes operable  after  a  few  weeks  of  Autolysate  treatment." 

All  this,  obviously,  might  have  been  written  of  the  effects  of 
administering  the  vegetable  proteins  instead  of  the  animal  pro- 
teins of  the  autolysates.  Note  also  the  following: 

"Klinger  regards  intravenous  injection  as  the  most  effectual 
route.  There  does  not  seem  to  be  any  danger  of  an  anaphylaxis, 
he  says,  but  sometimes  the  autolysates  seem  to  lose  their  power. 
This  can  be  avoided  by  changing  the  material." 

The  striking  analogy  here  with  what  has  been  pointed  out  in 
detail  again  and  again  in  the  present  book  about  wearing  out  the 
effect  of  one  Pro  teal  and  changing  to  another  will  be  obvious  to 
every  reader.  Even  more  striking  are  the  analogies  suggested  by 
the  theoretical  explanation  offered  as  to  the  action  of  the  auto- 
lysates, as  follows: 

"The  results  of  Klinger's  own  research  and  experience  confirm 
the  possibility  of  influencing  the  growth  of  a  tumor  by  injecting 
certain  products  of  the  breaking  down  of  albumin.  These  auto- 
lysates supply  the  body  with  ready-made  ferment  while  at  the 
same  time  exerting  a  stimulating  action  on  the  blood-producing 


246  THE   PROTEAL   TREATMENT   OF   CANCER 

tissues,  whipping  them  up  to  increased  production  of  the  tumor 
cell-destroying  substances.  As  cancers  consist  essentially  of  al- 
buminoid substances,  it  seems  evident  that  their  retrogression  and 
absorption  depend  on  the  intensification  of  certain  disintegration 
processes." 

Here,  it  will  be  observed,  the  ideas  which  furnish  the  essential 
thesis  of  the  present  monograph — to  the  effect  that  protein  an- 
tigens stimulate  the  blood-producing  tissues,  and  that  these  in 
turn  produce  the  substances  that  destroy  the  tumor  cell — are 
stated  as  if  they  were  matters  of  common  or  accepted  knowledge. 
If  Klinger  reached  these  conclusions  independently,  and  without 
having  seen  my  papers  of  October  and  November,  1914,  and 
Ocober  2,  1915,  his  estimate  will  obviously  have  peculiar  value 
by  way  of  corroboration. 

I  mention  this,  not  because  questions  of  priority  have  con- 
siderable significance  or  even  interest,  but  because  the  main  thesis 
involved  has  vast  importance,  and  because  the  judicious  reader 
cannot  fail  to  be  impressed  by  the  fact  that  certain  Swiss  physi- 
cians working  with  animal  proteins  should  have  obtained  results 
so  strikingly  in  accordance  with  results  obtained  by  American 
physicians  working  with  vegetable  proteins.  It  does  not  appear 
that  Klinger  recognizes  the  response  of  the  blood-forming  organs 
as  essentially  a  protein  reaction,  but  that  detracts  nothing  from 
the  corroborative  value  of  his  observations. 

My  own  work  has  been  carried  forward,  as  the  reader  is  well 
aware,  under  guidance  of  an  hypothesis — the  hypothesis,  namely, 
that  results  were  attained  through  the  administration  of  proteins 
or  protein  by-products,  as  such;  that  the  patient  immunized 
against  one  protein  may  be  given  a  stimulus  by  the  use  of  another 
protein,  and  ultimately  by  yet  another;  and  that  there  is  nothing 
mysterious  connected  with  the  matter,  except  in  so  far  as  all 
biological  processes  are  mysterious. 

It  is  vastly  important  that  this  thesis  should  be  sustained  or 
repudiated  at  the  earliest  possible  moment.  All  my  recent  ex- 
periences tend  to  confirm  the  thesis ;  to  establish  it  more  firmly  in 
my  mind.  In  bringing  forward  the  reports  of  other  workers, 
therefore,  as  I  am  doing  in  the  present  section,  the  only  thought 
is  to  present  to  the  reader  as  wide  an  array  of  evidence  as  possible, 
not  because  there  is  the  remotest  element  of  doubt  in  my  own 
mind  as  to  the  validity  of  the  argument,  but  because  I  am  aware 
that  the  discovery  in  itself  seems  so  simple  as  to  be  almost  un- 
believable; and  because,  therefore,  I  wish  to  fortify  this  in  the 
mind  of  the  reader  as  completely  as  data  at  present  available 
permit. 

It  is  a  familiar  experience  in  medicine  that  innovators  appear 
to  get  results  with  a  remedy  that  others  cannot  duplicate.  There- 


THE    PROTEIN    RESPONSE    INTERPRETED  247 

fore,  I  have  wished  to  show  that  the  protein  method  is  one  that  is 
in  no  wise  dependent  upon  the  operation  of  any  individual  or  com- 
pany of  individuals.  I  wish  to  show  that  any  physician  can 
utilize  the  method  and  get  initial  results.  I  wish  also,  however, 
to  emphasize  the  fact  that  the  initial  results  will  not  be  maintained 
in  the  vast  majority  of  cases,  if  a  single  protein  is  adhered  to, 
and  that  it  is  necessary  to  follow  up  the  method  along  scientific 
lines,  guided  by  results  not  only  clinical  but  microscopical  (with 
especial  reference  to  the  relative  status  of  the  corpuscles)  ;  and 
to  point  out  that  this  opinion  is  not  the  result  merely  of  my  own 
experience,  wide  though  that  be,  but  is  fortified  by  the  experience 
of  other  workers  with  proteins,  including  those  who  had  no 
definite  idea  as  to  the  real  character  of  the  work  they  were 
carrying  out. 

SECTION  VI. 
THE  PROTEIN  RESPONSE  INTERPRETED 

The  paper  of  October  2,  1915,  which  announced  to  the  medi- 
cal profession  the  introduction  of  a  fundamentally  new  method 
in  therapeutics, — namely,  the  use  of  non-specific  protein  antigens 
as  such, — as  interpreted  in  the  light  of  the  Proteomorphic 
theory,  had  to  do  specifically  with  the  interpretation  of  the  action 
of  non-toxic  vegetable  proteins  in  their  relation  to  malignant  neo- 
plasms, but  clear  intimations  were  given  that  the  therapeutic  prin- 
ciple believed  to  be  involved  had  much  wider  application.  The 
action  of  the  extract  was  explained  as  chiefly  due  to  its  protein 
content  (the  relatively  non-toxic  vegetable  proteins  acting  as  anti- 
gens to  stimulate  the  enzymic  activities  of  the  corpuscles  and  new 
corpuscle-production  by  the  cytogenic  apparatus),  and  the  con- 
clusion was  expressly  stated  that  the  remedy  "is  not  merely  a 
cancer  redemy ;  it  is  a  remedy  against  all  protein  infections." 

I  further  stated  the  belief  that  in  the  attempt  to  explain  the 
rationale  of  the  action  through  which  the  vegetable  proteins  bring 
about  a  beneficent  increase  in  the  armies  of  leucocytes  and  ery- 
throcytes,  "we  shall  gain  glimpses  of  an  entirely  new  field  of 
therapeutics,  and  shall  be  enabled  to  give  at  least  a  proximal  ex- 
planation of  the  exact  manner  of  action  of  a  remedy,  the  intro- 
duction of  which,  I  believe,  constitutes  the  inauguration  of  a 
method  that  must  in  future  rank  with  serum  therapy  and  vaccine 
therapy — if,  indeed,  it  does  not  altogether  outstrip  or  totally  sup- 
plant both  these  relatively  new  additions  to  the  equipment  of  the 
practical  physician." 

I  have  elsewhere  referred  to  the  sceptical  attitude  of  the  pro- 
fession toward  this  confident  prophecy.  It  will  be  obvious  from 


248  THE   PROTEAL   TREATMENT   OF   CANCER 

the  words  quoted,  however,  that  in  my  own  mind  the  matter  was 
perfectly  clear.  To  me  it  seemed  that  the  Proteomorphic  theory 
offered  through  basis  for  interpretation  of  the  observed  phe- 
nomena. It  has  been  observed  that,  following  the  hypodermic 
injections,  in  cases  of  inoperable  cancer,  pain  was  modified  or 
annulled,  the  malodor  disappeared,  and  in  many  cases  the  cancer 
mass  itself  was  modified  in  character  or  progressively  decreased 
in  size. 

I  had  not  only  observed  these  clinical  changes  at  first  hand, 
but  had  gathered  statistical  data  regarding  them  (published  in 
detail  in  a  subsequent  article  in  the  New  York  Medical  Journal 
of  November  13,  1915).  •  As  to  the  facts,  there  could  be  no  doubt. 
The  explanation  of  the  facts  seemed  to  me  equally  unequivocal. 
Scientific  caution  led  me  to  concede  that  some  other  constituent 
of  the  plant  extract  employed — for  example,  chlorophyll,  lipoids, 
or  chromophyl — might  in  a  measure  be  operative.  But  the  chief 
action  I  ascribed  unhesitatingly  to  the  protein  content;  and  the 
explanation  was  given  in  terms  of  the  Proteomorphic  theory,  in 
part  as  follows : 

It  is  well  known  that  foreign  proteins  of  whatever  character, 
when  introduced  into  the  parenteral  system,  constitute  antigens 
that  stimulate  the  body  to  the  producion  of  defensive  enzymes, 
that  tend  to  proteolyze  the  antigen  itself  and  to  neutralize  its 
toxic  products.  According  to  the  Proteomorphic  theory,  the  chief 
agents  in  the  production  of  these  proteolytic  and  antidotal 
enzymes  are  the  white  and  red  blood  corpuscles,  the  latter  being 
concerned  with  the  end  products  of  the  polypeptid  order.  Ac- 
cording to  the  theory,  large  numbers  of  the  red  corpuscles  them- 
selves are  destroyed  in  the  liver,  in  the  process  of  eliminating  the 
toxic  end  products  of  protein  metabolism  from  the  system.  This 
explains,  for  example,  the  pernicious  anaemia  that  may  result 
from  the  absorption  of  toxins  of  protein  origin,  as  in  bothrio- 
cephalus  poisoning. 

Similar  destruction  of  the  red  corpuscles,  in  their  attempt  to 
rid  the  body  of  toxins,  explains,  according  to  the  present  thesis, 
the  pernicious  anaemia  that  generally  accompanies  malignant  neo- 
plasms. The  animal  protein  cell  does  not  break  down  without  the 
production  of  toxic  molecules,  and  wherever  animal  proteins  of 
any  type  are  being  split  up  parenterally,  such  destruction  of  the 
red  corpuscles  must  occur,  with  the  result  that  the  cytogenic 
apparatus  may  finally  be  overtaxed  and  find  itself  unable  to  keep 
up  the  supply. 

It  seems  probable,  however,  that  vegetable  proteins,  notwith- 
standing their  chemical  similarity  to  animal  proteins,  are  less 
likely  to  produce  toxic  by-products  during  disintegration.  It  is  a 
familiar  doctrine  that  animal  proteins  rather  than  vegetable  are 


THE    PROTEIN    RESPONSE    INTERPRETED  249 

the  source  of  intestinal  putrefactions.  There  is  theoretical  war- 
rant, according  to  the  Proteomorphic  theory,  for  the  assumption 
of  the  less  toxicity  of  vegetable  proteins,  in  the  fact  that  they 
doubtless  have  constituted  the  food  of  our  ancestors  for  a  much 
longer  period  than  have  animal  proteins.  Probably  the  remote 
ancestors  of  men  were  eaters  of  vegetables  for  millions  of  genera- 
tions before  they  became  eaters  of  animal  foods.  And,  according 
to  the  thesis  under  discussion,  the  toxicity  of  any  type  of  protein 
is  directly  proportional  to  the  newness,  so  to  speak,  or  the  in  fre- 
quency with  which  the  organism  has  come  in  contact  with  it. 
Toxicity  is  not  a  thing  per  se,  but  a  matter  of  relativity.  In- 
herently, all  proteins  are  poisonous  to  every  organism  except  the 
one  producing  them.  A  few  drops  of  eel's  blood  injected  into 
the  veins  of  a  dog  will  cause  death. 

Doubtless  there  is  great  diversity  among  vegetable  proteins 
themselves  as  to  the  matter  of  toxicity ;  but  the  ones  actually  in- 
troduced are  of  a  type  to  produce  a  minimum  of  toxicity  while  at 
the  same  time  acting  as  vigorous  antigens,  stimulating  the  cyto- 
genic  mechanisms  to  the  rapid  production  of  white  and  red  blood 
corpuscles.  Doubtless  these  corpuscles  proteolyze  the  vegetable 
protein  itself,  but  in  so  doing  the  red  corpuscles  are  not  destroyed 
in  large  numbers,  because  they  have  a  minimum  of  toxic  by- 
products to  deal  with. 

The  large  mononuclear  leucocytes,  which  have  been  shown  to 
produce  enzymes  that  are  peculiarly  active  in  the  splitting  up  of 
cancer  cells,  are  usually  found  to  increase  very  markedly  in  the 
blood.  There  is  also  increase  of  the  lymphocytes,  which  are 
credited  with  an  active  share  in  the  splitting  up  of  animal  pro- 
teins, and  of  the  eosinophiles.  The  enzymes  generated  by  these 
protein  fighters  begin  the  disintegration  of  cancer  cells  (which, 
because  of  their  embryonic  character,  are  more  susceptible  to  dis- 
integration than  are  the  cells  of  normal  tissue),  and  the  products 
of  such  disintegration  are  liberated  into  the  blood  stream,  where 
the  red  corpuscles,  now  banded  in  adequate  numbers,  continue 
the  work  of  proteolysis  and  elimination. 

Of  course,  the  disintegrating  cancer  cells  liberate  toxic  mole- 
cules, and  in  dealing  with  these  the  red  corpuscles  are  of  neces- 
sity destroyed  in  large  numbers  in  the  liver.  But  this  temporary 
reduction  in  the  numbers  of  the  erythrocytes  is  compensated 
almost  immediately  by  the  stimulative  effects  of  a  succeeding 
dose  of  protein,  so  that  unless  the  breaking  down  of  cancer 
tissues  goes  forward  very  rapidly  indeed,  the  aggregate  count  of 
red  cells  increases  from  day  to  day.  It  is  not  unusual  to  find 
the  count  above  five  million,  after  the  treatment  is  well  estab- 
lished. The  enzyme-forming  capacity  of  the  red  cells  is  probably 
increased  proportionately. 


250  THE   PROTEAL  TREATMENT  OF  CANCER 

The  chill  and  rise  of  temperature  that  mark  the  characteristic 
reaction,  and  serve  as  guides  to  the  clinician,  probably  mark 
the  period  when  the  cumulative  action  of  the  leucocytes  has 
taxed  the  blood  with  more  polypeptid  by-products  than  the  red 
cells  can  for  the  moment  handle,  so  that  the  ranks  of  the  latter 
have  been  momentarily  depleted,  and  the  chill  gives  warning 
that  the  system  is  feeling  the  effects  of  toxicity.  But  the  rise  of 
temperature  is  compensatory,  since  this  in  itself  stimulates  the 
activity  of  the  cytogenic  apparatus,  so  that  in  a  short  time  there 
are  usually  enough  of  the  corpuscular  defenders  present  to  take 
care  of  the  obnoxious  protein  products. 

If  compensation  does  not  take  place  quickly,  the  delay  serves 
as  a  warning  to  the  clinician  that  he  should  let  a  longer  interval 
elapse  before  giving  the  next  dose,  or  administer  the  remedy  in 
smaller  doses. 

If  the  foregoing  reasoning  is  accepted,  it  is  clear  that  we  can 
form  a  tolerably  vivid  mental  picture  of  the  processes  through 
which  the  regression  of  the  malignant  tumor  is  brought  about 
under  the  influence  of  the  vegetable  protein  antigens.  The  ob- 
served phenomenon  of  the  cessation  of  pain,  which  is  one  of  the 
most  uniform  and  gratifying  immediate  results,  is  explicable  as 
due  to  the  softening  and  disintegration  of  the  peripheral  cancer 
cells  that  have  encroached  upon  the  nerve  fibrils.  The  time  re- 
quired for  the  pain-annulling  effects  to  make  themselves  manifest 
would  appear  to  depend  upon  the  exact  site  of  the  cancer,  and 
the  extent  to  which  its  cells  have  involved  the  nerves.  As  the 
cancer  tissue  steadily  regresses,  it  is  withdrawn  more  and  more 
from  interference  with  the  nerves,  and  the  cessation  of  pain  is 
lasting. 

There  is  very  commonly  experienced  a  sensation  of  gnawing 
or  digging  at  the  site  of  the  tumor,  which  is  not  exactly  agreeable, 
but  which  the  patient  cheerfully  tolerates  because  he  regards  it, 
doubtless  quite  correctly,  as  an  evidence  that  salutary  changes 
are  taking  place  within  the  tissues  of  the  neoplasm. 

The  cessation  of  odor  in  superficial  ulcerative  neoplasms  or 
in  the  discharge  from  uterine  or  other  masses,  is  readily  under- 
stood, according  to  the  present  thesis,  as  due  to  the  activities  of 
the  hitherto  depleted  but  now  adequate  army  of  red  blood 
corpuscles.  The  decomposition  products  that  produce  the  bad 
odor  are  precisely  of  the  character  of  the  protein  products  that, 
according  to  hypothesis,  the  red  blood  corpuscles  deal  with 
habitually.  The  odor  was,  therefore,  directly  due  to  the  in- 
adequacy of  the  supply  of  red  blood  corpuscles,  and  it  disappears 
almost  as  a  matter  of  course  when  this  defect  is  fully  compensated. 


VEGETABLE   PROTEIN    IN    CANCER   TREATMENT  251 

SECTION   VII. 

VEGETABLE  PROTEINS  IN  CANCER  TREATMENT 

It  seems  perfectly  clear,  and  even  obvious  now,  in  the  light  of 
later  experience,  that  the  above  interpretation  is  valid.  But  at 
the  time  when  it  was  made,  the  interpretation  was  fortified  by  my 
own  belief  in  the  Proteomorphic  theory  rather  than  by  demonstra- 
tive evidence.  I  was  presently  able,  however,  to  bring  forward 
substantive  evidence  of  more  tangible  character  through  de- 
velopment of  a  new  series  of  antigens  of  known  composition, 
made  for  the  express  purpose  of  testing  the  assumption  that  the 
observed  action  of  the  original  extract  above  referred  to  was 
essentially  due  to  its  protein  content.  An  analytical  laboratory 
investigation  had  been  made  in  which  it  was  shown  that  each  of 
the  twelve  constituents  contributed  a  fractional  quantity  of  pro- 
tein to  the  extract ;  but  that  the  major  part  of  the  protein  came 
from  the  mustard  seed,  as  might  be  expected. 

It  was  at  first  contemplated  to  make  clinical  observations  with 
each  of  the  individual  proteins,  to  determine  whether  any  one  of 
them  or  any  particular  combination  of  them  had  exceptional  value 
in  stimulating  a  characteristic  physiological  response  of  the  or- 
ganism. But  since  this,  obviously,  would  involve  an  enormous 
expenditure  of  time  and  labor,  it  was  thought  that  a  short-cut 
might  be  effected  by  making  the  provisional  assumption  that  any 
foreign  protein  of  non-toxic  character  might  produce  an  effective 
enzymic  response.  Theoretically,  in  the  light  of  the  Proteomor- 
phic theory,  it  should  be  so.  I  determined  to  find  out  whether 
it  was  so  in  practice. 

A  large  variety  of  vegetable  substances  were  used  as  the  source 
of  new  extracts,  among  others  alfalfa  seed,  alfalfa  meal,  hemp 
seed,  and  rape  seed,  and,  later,  clover  seed,  cotton  seed,  timothy 
seed  and  various  others,  and  sundry  foodstuffs. 

The  practical  stimulus  to  the  development  of  the  new  proteins 
was  the  fact  that  in  a  large  number  of  cases  patients  suffering 
from  inoperable  cancer  who  had  responded  strikingly  to  the  treat- 
ment with  the  original  combination  of  vegetable  proteins  came 
finally  to  a  seemingly  static  period,  at  which  they  snowed  notable 
improvement  over  their  previous  condition,  yet  now  seemed  no 
longer  to  respond  actively  to  the  stimulus  of  the  remedy.  Seem- 
ingly they  were  immunized  against  further  enzymic  response  to 
the  particular  proteins  in  question.  But  there  seemed  to  be  at 
least  a  possibility  that  they  might  take  on  fresh  response  if  new 
proteins  were  administered. 

This  expectation  was  justified  in  a  considerable  number  of  cases 
to  which  the  new  proteins  have  been  administered,  singly  or  in 


252  THE   PROTEAL   TREATMENT   OF   CANCER 

combination,  during  subsequent  months.  It  was  found  that 
patients  who  were  virtually  immunized  to  the  combined  proteins, 
taking  large  doses  without  tangible  response,  showed  marked 
anaphy  lactic  reaction  when  small  doses  of  the  new  proteins  were 
administered.  Such  being  the  case,  it  was  not  surprising  that 
there  should  be  a  corresponding -modification  of  clinical  symptoms 
and  a  characteristic  modification  of  the  differential  blood  count 
to  which- 1  shall  refer  more  in  detail  in  a  moment. 

In  the  New  York  Medical  Journal  of  November  13,  1915,  I 
summarized  the  preliminary  results  attained  in  the  treatment  of 
766  cases  of  inoperable  cancer  by  152  physicians  using  the  orig- 
inal vegetable  protein  extract. 

These  were  all  cases  of  far-advanced  malignancy,  mostly  post- 
operative. Many  of  them  had  been  X-rayed  and  radiumed.  All 
were  pronounced  inoperable  before  the  protein  treatment  was 
undertaken ;  and  this  treatment  was  used  to  the  exclusion  of  any 
other.  The  preliminary  results,  as  tabulated  in  the  article  in 
question,  showed  that  16.5  per  cent,  of  the  cases  in  question  were 
reported  as  having  died ;  19.5  per  cent,  as  being  unimproved ;  and 
64  per  cent,  as  being  improved  to  a  greater  or  less  extent. 

Following  the  summary,  this  comment  was  made : 

"As  most  of  the  patients  in  question  have  been  under  treat- 
ment for  periods  of  only  from  two  weeks  to  two  months ;  and 
as  by  far  the  greater  majority  of  them  were  in  a  very  desperate 
state  at  the  time  when  the  treatment  was  undertaken,  it  must  be 
admitted  that  this  is  a  very  gratifying  showing.  It  is  perhaps 
unnecessary  to  add  that,  despite  the  favorable  showing,  most  of 
these  cases  are  not  as  yet  at  a  stage  where  prediction  can  be  made 
as  to  the  ultimate  outcome." 

It  will  be  of  interest,  I  think,  to  introduce  here  in  tabular  form 
a  summary  of  the  reports  made  by  a  group  of  co-operating  physi- 
cians in  response  to  a  questionnaire  I  sent  out  under  date  of 
October  25,  1915.  The  letter  was  accompained  by  a  blank  form, 
covering  details  as  to  the  type  of  cases  of  inoperable  cancer 
treated,  and  the  general  and  special  results  observed. 

This  form  was  sent  to  about  275  physicians,  located  in  various 
parts  of  the  United  States.  In  the  course  of  a  few  days,  replies 
were  received  from  144  physicians.  This  was  perhaps  as  high  a 
percentage  as  could  be  expected.  The  number  is  large  enough  to 
give  fairly  satisfactory  statistical  data;  and  there  is  no  reason  to 
believe  that  the  essential  character  of  the  report  would  be  changed 
had  the  entire  number  responded.  Be  that  as  it  may,  the  reports 
received  are  printed  here  serially,  each  bearing  the  number  that 
the  physician's  name  bears  in  my  office  files.  Results  are  tentative, 
but  the  aggregate  report  is  at  least  highly  suggestive. 


VEGETABLE    PROTEIN    IN    CANCER   TREATMENT 

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254  THE   PROTEAL   TREATMENT  OF   CANCER 

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VEGETABLE    PROTEIN    IN    CANCER    TREATMENT  255 


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THE   PROTEAL   TREATMENT   OF   CANCER 


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VEGETABLE  PROTEIN  IN  CANCER  TREATMENT        257 

If  we  summarize  the  above  table,  and  condense  the  findings 
into  a  single  table  aggregating  total  results,  we  have  the 
following : 

Total  number  of  physicians,  144,  residing  in  37  states  and  in 
several  provinces  of  Canada;  including  63  members  of  the 
American  Medical  Association  and  29  other  physicians  who  are 
members  of  State  Medical  Associations. 

Total  number  of  cases  treated,  284;  of  which  209  were  carci- 
nomas, 52  epitheliomas,  and  17  sarcomas,  6  being  unclassified. 

General  results  of  treatment: 

(1)  Died,  43,  or  15.2  per  cent,  of  the  total  cases. 

(2)  Unimproved,  60  (21  deteriorated  and  39  unchanged),  or 
21.3  per  cent,  of  total  cases. 

(3)  Improved,  179,  or  63.1  per  cent. 

(4)  Of  favorable  prognosis,  out  of  danger,  or  clinically  well, 
48,  or  16.2  per  cent,  of  total  cases. 

(5)  Unclassified  as  to  general  resuks,  two  cases. 

Results  as  to  special  symptoms: 

(1)  Pain  present  in  221  cases;  favorably  modified  by  treat- 
ment in  171  cases,  or  77.4  per  cent. 

(2)  Offensive    discharge,    present    in    111    cases;    favorably 
modified  in  96  cases,  or  85.6  per  cent. 

(3)  General  health  of  patient:    Seemingly  uninfluenced  by 
treatment  in  77  cases ;  favorably  modified  as  to  appetite,  sleeping, 
color,  weight  or  strength  in  180  cases,  or  70  per  cent. 

(4)  Mental  attitude:     Seemingly  uninfluenced  in  74  cases; 
favorably  modified  in  180  cases,  or  71  per  cent. 

(5)  Condition  of  the  neoplasm:     Seemingly  uninfluenced  in 
79  cases,  or  27.8  per  cent. ;   favorably  modified  in   171,  or  60 
marked  regression  in  size  in  76  cases,  or  26.8  per  cent. 

Dealing,  as  the  statistics  do,  with  supposedly  hopeless  cases, 
in  the  presence  of  which  the  physician  has  hitherto  stood  power- 
less, and  with  symptoms  mostly  not  susceptible  of  amelioration 
by  any  agency  hitherto  available,  this  is  a  showing  that  is  amazing 
and  enheartening. 

In-  the  period  of  thirty  -months  that  has  elapsed  *  since  the 
reports  thus  tabulated  were  received,  I  have  been  constantly  in 
touch  with  a  considerable  number  of  physicians  who  'have  used 
the  Proteals  in  the  treatment  of  inoperable  cancer.  Their  reports 
have  come  in  the  form  usually  \}f  personal  letters, — letters  not  de- 
signed in  any  case  for  publication,  and  for  the  most  part  written 
in  the  interest  of  the  individual  patient,  asking  advice  as  to  some 
detail  of  treatment  very  commonly,  and  containing  expressions 
of  opinion  as  to  the  progress  of  the  case  of  precisely  the  character 
a  practitioner  would  make  in  seeking  the  advice  of  a  special  con- 
sultant. 


258          THE  PROTEAL  TREATMENT  OF  CANCER 

It  must  be  evident,  I  think,  that  reports  made  under  such  cir- 
cumstances have  peculiar  value.  In  the  nature  of  the  case,  they 
are  candid,  frank,  and  uncolored. 

On  the  other  hand,  it  must  be  borne  in  mind  that,  by  the  same 
token,  these  men  are  for  the  most  part  not  specialists  of  wide 
experience  in  the  treatment  of  cancer  cases.  A  number  of  them 
are  such,  to  be  sure,  but  in  the  main  the  physicians  of  the  group 
under  consideration  are  general  practitioners.  But  in  a  way 
that  makes  their  testimony  all  the  more  important,  inasmuch  as 
it  shows  what  the  new  line  of  treatment  may  be  expected  to 
accomplish  in  the  hands  of  the  average  practitioner.  One  of  the 
greatest  merits  of  the  Proteal  treatment  is  that  it  enables  isolated 
physicians,  in  the  remotest  hamlets,  to  do  something  tangible  and 
definite  toward  ameliorating  the  condition  of  the  cancer  patient 
who  has  passed  beyond  the  reach  of  the  surgeon. 

Thanks  to  the  new  treatment,  the  most  inexperienced  practi- 
tioner can  do  more  to-day  for  the  amelioration  of  the  condition 
cf  a  late  stage,  inoperable  cancer  case  that  could  hitherto  be 
accomplished  by  the  most  experienced  practitioner  in  the  best 
metropolitan  cancer  hospital. 

The  substantial  unanimity  of  opinion  as  to  the  character  of 
results  attained  in  their  own  practice  by  some  hundreds  of  phy- 
sicians scattered  about  the  country,  and  in  foreign  countries,  is 
so  striking  a  phenomenon  that  it  is  susceptible  of  but  one  inter- 
pretation. It  is  impossible  that  all  these  men  should  be  mistaken. 
Their  individual  observations,  when  aggregated,  pile  mountain 
high  the  evidence  that  the  proteal  treatment  has  remarkable  effect 
in  relieving  pain  of  the  inoperable  cancer  subject;  removing  the 
bad  odor  of  cancerous  discharges;  improving  the  general  health 
of  the  patient ;  and  conspicuously  modifying  the  condition  of  the 
malignant  neoplasm. 

After  carefully  scrutinizing  the  evidence,  it  is  difficult  to  avoid 
the  conclusion  that  these  beneficial  effects  of  the  proteal  treat- 
ment, in  varying  degree,  may  be  observed  in  an  overwhelming 
proportion  (not  less,  in  my  opinion,  than  80  per  cent.)  of  cases 
of  inoperable  cancer,  wherever  located,  in  which  the  remedy  is 
administered  in  .suitable  doses. 

This,  it  will  be  observed,  postulates  nothing  as  to  the  ultimate 
effects  of  the  treatment.  It  says  nothing  as  to  the  "cure"  of 
cancer.  As  to  that,  I  shall  have  something  to  say  in  detail  a 
little  later.  Here  it  suffices  to  note  that  the  records  under  con- 
sideration tell  of  definite  and  unequivocal  improvement  of  the 
most  tangible  character  in  a  large  proportion  of  cases ;  such  im- 
provement amounting  in  a  certain  number  of  cases  to  seeming 
clinical  recovery. 


THE  BLOOD  IN  CANCER  SUBJECTS  259 

SECTION  VIII 
THE  BLOOD  IN  CANCER  SUBJECTS 

It  will  be  recalled  by  those  who  have  read  the  original  presenta- 
tion of  the  Proteomorphic  Theory  that  the  theory  ascribes  to  the 
lymphocytes  in  the  blood  the  function  of  beginning  the  decom- 
pounding of  protein  molecules.  It  will  be  recalled  also  that  ex- 
periments (of  Vaughan)  are  cited  which  seem  to  show  that  the 
large  monocytes  have  power  to  produce  enzymes  that  bring  about 
the  decompounding  of  cancer  cells. 

It  is  of  pecular  interest,  then,  to  inquire  as  to  the  modifications 
of  the  blood  count  that  are  associated  with  the  cancerous  con- 
dition, and  the  further  modifications  that  are  brought  about  by 
therapeutic  application  of  protein  antigens. 

It  has  long  been  recognized  by  pathologists  that  there  are 
marked  modifications  of  the  blood  count  in  nearly  all  cases  of 
malignant  disease.  Most  observers  have  been  content  to  note  the 
reduction  of  the  haemoglobin  index  and  of  the  red  blood  count, 
and  the  marked  leucocytosis  that  usually  characterizes  the  condi- 
tion, at  least  in  its  advanced  stages.  A  number  of  observers, 
however,  have  fortunately  made  more  elaborate  studies,  and  rec- 
ords are  available  in  the  literature  covering  a  considerable  body 
of  cases  in  which  complete  blood  counts  were  made  that  furnished 
the  basis  for  a  comparative  study  in  connection  with  the  original 
observations  that  I  am  about  to  record. 

Dr.  Price  Jones  has  published  detailed  results  of  the  study  of 
29  cases  of  cancer,  including  carcinomas  of  the  breast,  stomach, 
intestine,  generative  organs,  tongue,  and  larynx,  and  variously 
located  sarcomata.  His  results  show  an  average  of  3,838,000  red 
blood  cells  and  10,409  white  cells  to  the  cubic  millimeter.  The 
differential  count  showed  73.7  per  cent,  of  polynuclears,  10.38 
per  cent,  large  monocytes,  and  13.6  small  lymphocytes.  Eosino- 
philes  and  basophiles  are  not  recorded,  but  by  exclusion  are  shown 
in  the  aggregate  to  represent  2.32  per  cent,  of  the  leucocyte  census. 

Another  interesting  series  of  cases  comprises  cancer  in  which 
there  were  bone  matastases,  recorded  by  different  observers,  and 
aggregating  22  cases  fully  reported.  Here  the  average  red  blood 
count  was  found  to  be  2,808,000 ;  the  average  white  blood  count, 
14,214  (increased  by  the  presence  of  a  few  cases  in  which  the 
leucocytosis  was  extreme).  The  differential  count  shows  58.11 
per  cent,  polynuclears ;  14.89  per  cent,  large  monocytes ;  25.86  per 
cent,  small  lymphocytes;  0.87  per  cent,  eosinophiles ;  and  .027 
per  cent,  basophiles.  A  considerably  modified  average  is  found 
if  we  consider  only  the  first  count  in  each  of  the  22  cases,  the  re- 
sult being:  red  corpuscles,  2,744,000;  white  corpuscles,  11,500 


260 


THE  PROTEAL  TREATMENT  OF  CANCER 


(the  aberrant  case  being  omitted);  poly  nuclear  s,  65  per  cent.; 
large  monocytes,  11.7  per  cent;  small  lymphocytes,  22  per  cent.; 
eosinophiles,  1  per  cent. 

These  results  may  be  compared  with  the  table,  herewith  pre- 
sented, of  our  own  untreated  cases.  It  will  be  seen  that  there  is 
close  general  agreement.  I  would  call  special  attention  to  the 

TABLE  II— THE  BLOOD  COUNT  IN  CANCER 
TWENTY-NINE  CASES  OF  DR.  PRICE  JONES  \t  THE  MIDDLESEX  HOSPITAL,  ENGLAND 


Nature  of  Case 

No. 
of 
Cases 

Red 
Blood 
Corpuscles 

White 
Blood 
Cor- 
puscles 

Poly- 
nuclears 

MONONUCLEARS 

Large 

Small 

9 
7 
2 
6 
1 
1 
4 

4,230,000 
3,770,000 
4,600,000 
4,160,000 
3,780,000 
2,400,000 
4,490,000 

10,400 
9,700 
14,600 
14,280 
18,600 
6,300 
10,930 

7,115 
7,070 
11,478 
10,038 
13,974 
4,365 
.  7,847 

1,324 
835 
1,446 
1,671 
1,711 
819 
1,158 

1,661 
1,598 
1,490 
2,103 
2,845 
1,091 
1,694 

Card,  of  the  Stomach  
'      of  the  Intestine  

'      Generative  Organs  
'      of  the  Tongue  

"      of  the  Larynx  

Weighted  averaged  of  29  cases. 

3,838,000 

10,409 

7,664 

73.7% 

1,077 
10.38% 

1,421 
13.6% 

TABLE  III— TWENTY-TWO  CASES  OF  CANCER  WITH  BONE  METASTASES 
REPORTED  BY  DIFFERENT  PHYSICIANS 


Observer 

Hemo- 
globin 

Red 
Blood 
Cor- 
puscles 

White 
Blood 
Cor- 
puscles 

Poly- 

nu- 
clears 

MONONUCLEARS 

Eosino- 
philes 

Baso- 

philes 

Large 

Small 

1.  Hawley 

75 
62 
49 

35' 
60 
15 
25 
60 
21 
40 
105 
46 
65 
50 
115 
85 
56 

45' 
20 
50 

3,172,000 
2,751,000 
2,300,000 
1,056,000 
1,600,000 
1,940,000 
1,550,000 
1,825,000 
4,320,000 
900,000 
1,984,000 
4,452,000 
2,168,000 
4,760,000 
4,920,000 
4,725,000 
5,615,000 
3,850,000 
3,020,000 
2,150,000 
1,000,000 
3,000,000 

7,300 
2,500 
6,700 
10,200 
14,000 
3,500 
20,000 
9,100 
19,700 
9,220 
16,400 
7,600 
6,000 
10,800 
9,000 
3,700 
8,500 
20,300 
120,000 
22,000 
30,000 
6,000 

63.0 
56.4 
54.0 
78.0 
63.0 
60.0 
66.0 
48.5 
86.1 
64.5 
82.0 
58.6 
66.0 
50.7 
68.9 
51.0 
68.0 
60.0 
96.17 
59.0 
78.8 
56.7 

10.0 
20.0 
9.2 
9.5 
17.6 
14.0 
12.0 
31.4 
7.0 
19.0 
8.7 
4.6 
8.2 
17.4 
6.5 
4.6 
11.4 
14.0 
1.25 
8.5 
15.6 
12.7 

27.0 
19.6 
36.2 
11.0 
16.7 
21.0 
22.0 
19.2 
6.2 
15.0 
8.2 
35.1 
19.0 
31.2 
23.3 
42.2 
21.4 
23.0 
2.16 
31.0 
4.6 
30.5 

0 
1.6 
0.6 
1.6 
0.7 
4.0 
0 
1.0 
0.7 
1.0 
1.2 
0.8 
0 
0.6 
0.8 
0.4 
0.2 
3.0 
0.42 
1.0 
0.5 
0.1 

0 
0 
0 
0 
0 
0 
0 
0 
0 
0.5 
0 
1.6 
0 
0 
0.5 
1.8 
0 
0 
0 
0.5 
0 
0 

2.  Harrington  
8.  Houston 

4.  Parkes  
6.  Harrington  
6.  Parmentier  
7.  Wolfer 

8.  Kurpjuweit  
9.  Kurpjuweit  
10.  Frese 

11.  Schleip  
12.  Schleip  .. 

13.  Naegeli... 

14.  Ward  
15.  Ward... 

16.  Ward 

17.  Ward  
18.  Ward  
19.  Kast  
20.  Turnbull  
21.  Hirschfeld  
22.  Bloch  

53.3 

2,744,000 

11,500 

65.26 

11.7 

22.06 

1.0 

0.2 

column  showing  the  percentages  of  large  mononuclear  leucocytes. 
Recalling  that  in  normal  blood  the  large  monocytes  number  only 
2  or  3  per  cent.,  as  a  rule,  with  perhaps  5  per  cent,  as  maximum, 
it  will  be  noted  that  in  Price  Jones'  series  of  cases  these  cells  num- 
ber 10.35  per  cent,  of  all  leucocytes ;  in  22  cases  of  bone  metasta- 


THE  BLOOD  IN  CANCER  SUBJECTS 


261 


ses,  as  first  counted,  they  number  11.7  per  cent.;  in  one  of  our 
series  (26  cases)  they  number  13.5  per  cent.,  and  in  another  of  our 
series  (22  cases)  they  number  14.05  per  cent.  It  should  be  under- 
stood that  the  large  mononuclear  leucocytes  do  not  constitute  a 
homogenous  group.  They  include,  in  an  ordinary  cancer  case,  not 
only  large  lymphocytes  and  normal  large  monocytes  (the  macro- 


TABLE  IV — ORIGINAL  CASES 
THH  BLOOD  COUNT  m  26  UNTREATED  CASES  OP  INOPERABLE  CANCER 


Case  No.  | 

Name 

Nature  of  Case 

j 

Red 
Blood 
Corpus- 
des 

White 
Blood 
Cor- 
pus- 

cles 

ll 

Mono- 
nucleara 

it 

1 

Large 

Small 

846 
361 
378 
335 
310 
394 
349 
333 
316 
356 
375 
327 
358 
224 
325 
344 
362 
331 
312 
355 

341 
339 

Mrs.  C.... 
Mr.  C  
Mrs.  DeB.. 
MissD  
Mr.  E  
Mrs.L..... 
Mrs.  G  
Mrs.H.... 
Mr.  K  
Mr.  L  
Miss  Me... 
MisaM.... 
Mr.  U  
Mrs.S  
Mr.  S  
Mrs.S  
Mrs.  St.... 
Mr.  S  
Mrs.  Y  
Mrs.S  
Mr.  M  
Mr.  G  
Dr.  L  
Dr.  McG.. 
Mr.  P  
Mrs.T  

Card,  of  Breast... 
"       "  Jaw 

90 
90 
100 
80 
65 
100 
95 
85 
75 
85 
90 
90 
95 
95 
85 
90 
85 
70 
46 
85 
45 
90 
100 

95 

85 

4,630,000 
4,568,000 
4,272,000 
2,464,000 
3,920,000 
5,280,000 
4,564,000 
3,824,000 
4,096,000 
4,640,000 
3,872,000 
5,160,000 
5,272,000 
5,088,000 
4,288,000 
4,684,000 
4,016,000 
3,744,000 
2,730,000 
3,376,000 
1,424,000 
5,360,000 
4,096,000 

4,992,000 
4,920,000 

9,320 
6,230 
8,000 
10,650 

9,566 
7,700 
8,650 

9,880 
7,880 
9,220 
7,550 
9,000 
7,240 
9,220 
8,100 
9,780 
16,600 
8,660 
11,550 
8,430 
10,000 

9,800 
9,680 

63 
77 
57 
70.6 
82 
65.5 
46.6 
50 
61 
75.5 
70.6 
64 
52.5 
78 
77 
80.6 
71.3 
67 
66 
74.3 
68 
57 
67 
79.3 
62 
53.3 

12 
9.6 
18.3 
8.6 
11 
10 
13.6 
19 
23 
12.3 
13.3 
12.6 
20.75 
13 
8 
12.6 
13 
10 
16 
14.3 
8 
20 
13.5 
9 
9 
21.3 

25 
13 
21.6 
7.6 
6 
20 
39 
28 
15 
12.3 
14.6 
21.6 
21.5 
6.5 
15 
6.6 
15 
23 
16 
10.3 
22 
21.5 
9.5 
6.6 
22 
25 

0 
.3 
3 
2.6 
1 
4 
.6 
3 
1 
0 
1.3 
1.6 
4.75 
2.5 
0 
0 
0 
0 
2 
1.3 
2 
1.5 
10. 
4.6 
7 
0.3 

0 
0 
0 
0.3 
0 
0.5 
0 
0 
0 
0 
0 
0 
0.5 
0 
0 
0 
0.6 
0 
0 
0 
0 
0 
0 
0 
0 
0 

"       "Uterus  
"       "  Breast 

"       "  Bladder  
"  Breast  

"       "  Uterus  
"  Breast 

Epithe.  of  Palate  
Card,  of  Stomach  
"  Breast  
"       "Mediastinum.. 
Sarc.  of  Peritoneum  
Epithelioma  
Card,  of  Larynx  
"       "  Breast 

"       "  Coscum  
Mixed  Parotid  Cancer... 
Card,  of  Uterus  
"       "Intestine  
Doubtful  Diagnosis  
Card,  of  Uterus  

Ep.  of  Tongue  
Card,  of  Stomach  

Average  for  abov 
Average  for  22  ca 
Weighted  average 
Unweighted     " 

e26  cases  
ses  in  Table  VI 

81.4 
81.9 
s:}.2 
73.2 

4,258,000 

4,271,000 
4,264,000 
3,777,000 

9,240 
8,840 
9,080 
10,000 

67.5 
67.95 
67.72 
68.6 

13.5 
14.05 
13.77 
12.45 

17 

16 
16.6 
17.16 

2 
1.69 
1.8 
1.56 

.07 
.07 
.07 
.11 

a  for  48  cases  
"    99     "    

The  above  26  blood  counts  of  cases  of  inoperable  cancer  constitute  a  fairly  representative 
group,  presented  here  together  because  they  chance  to  be  cases  in  which  only  a  single  blood 
count  was  made.  They  are  otherwise  unselected.  The  averages  of  this  group  may  advanta- 
geously be  compared  with  those  of  a  second  group  of  untreated  cases  detailed  in  Table  VI.  A 
combination  of  these  charts  gives  the  averages  for  48  untreated  cases  of  inoperable  cancer. 
For  purposes  of  comparison,  the  averages  of  the  29  cases  of  Price  Jones  and  the  22  cases  of 
bone  metastnses  reported  by  various  investigators  are  also  presented.  It  will  be  seen  that 
there  is  dose  general  agreement.  The  relatively  low  red  corpuscle  count  in  the  bone  cases  may 
perhaps  be  due  in  part  to  direct  involvement  of  the  marrow.  The  Price  Jones  cases  were 
hospital  cases.  The  original  cases  were  ambulatory,  although  late  stage  inoperables.  Thus 
we  have  a  fairly  representative  group  of  99  cases,  and,  in  so  far  as  any  generalizations  are 
justified  from  so  small  a  number,  we  may  take  the  grand  average  as  suggesting  a  typical  blood 
picture  in  advanced  stages  of  the  cancerous  condition. 

phages  of  Metchnikoff),  but  myeloctyes  (neutrophile,  eosinophile, 
and  occasionally  basophile),  leucoblasts,  and  lymphoidocytes. 
For  the  moment,  however,  it  will  be  convenient  to  group  all  of 
these  together,  in  consideration  of  their  probable  similarity  of 
origin,  and  their  obvious  similarity  of  structure, 


262  THE  PROTEAL  TREATMENT  OF  CANCER 

Striking  the  (unweighed)  average  for  these  99  cases,  we  find 
the  large  mononuclears  (of  these  various  groups)  aggregated  to 
represent  12.45  per  cent,  of  the  total  leucocyte  count.  This  is 
about  two  and  a  half  times  the  normal  maximum  percentage ;  and 
it  would  appear  that  we  may  accept  some  such  modification  as 
this  of  the  large  monocyte  count  as  typical  of  advanced  cases  of 
malignant  neoplasms.  Individual  cases,  as  a  matter  of  course, 
show  exceptions,  but  there  appear  not  to  be  more  than  five  or 
six  cases  in  the  entire  99  in  which  the  count  of  large  monocytes 
was  found  as  low  as  the  normal  maximum  limit. 

We  are  justified,  then,  I  think,  in  regarding  a  marked  increase 
of  the  large  monocytes  as  a  typical  manifestation  of  the  presence 
of  malignant  neoplasms  in  an  advanced  stage.  These  clinical 
observations  in  the  human  subject  find  support,  it  may  be  added, 
in  Price  Jones'  observations  of  cancerous  mice  in  which  also  a 
very  marked  increase  of  the  large  monocytes  was  noted.  It  should 
be  observed,  however,  as  having  interest  in  another  connection, 
that  the  percentage  of  large  monocytes  in  the  blood  of  the  normal 
mouse  is  far  higher  than  in  the  human  subject.  The  figures 
given  by  Price  Jones  are,  for  normal  mice,  21.5  per  cent.;  for 
cancerous  mice  32.2  per  cent,  of  the  total  leucocyte  count. 

The  question  at  once  arises  as  to  whether  the  observed  increase 
of  large  monocytes  in  the  cancerous  condition  is  to  be  regarded 
as  a  part  of  the  disease  process,  or  whether,  on  the  other  hand, 
it  manifests  a  salutary  modification  indicating  nature's  attempt  to 
combat  the  invasion  of  the  lawless  cancer  cells. 

In  view  of  the  known  functions  of  the  leucocytes  in  guarding 
the  body  against  bacterial  invasions,  we  may,  I  think,  unhesitat- 
ingly accept  the  increase  of  leucocytes  in  general  in  the  cancerous 
condition,  and  of  the  large  monocytes  in  particular,  as  represent- 
ing a  salutary  process.  The  fact  that  Vaughan's  experiments 
showed  that  enzymes  produced  by  the  large  monocytes  bring  about 
at  least  partial  decompounding  of  cancer  cells  naturally  comes  to 
mind  in  considering  the  observed  fact  of  the  increase  of  these 
monocytes  in  the  cancer  subject. 

It  seems  at  least  a  justifiable  inference  that  the  presence  of  the 
cancer  cells  has  directly  stimulated  the  production  of  large  mono- 
cytes, just  as  the  presence  of  foreign  pathogenic  bacteria  stimu- 
lates the  increased  production  of  phagocytic  polymorphs. 

If  this  view  is  accepted,  it  is  permissable  to  suppose  that  in  a 
very  large  number  of  cases  incipient  malignant  neoplasms  are 
nipped  in  the  bud,  so  to  speak,  by  the  activities  of  the  large  mono- 
cytes ;  and  that  the  presence  of  a  tangible  cancer  demonstrates  the 
fact  that,  in  this  individual  case,  the  body  has  been  unable  to  pro- 
duce the  defending  corpuscles  in  adequate  numbers  to  overmaster 
the  invading  cancer  cells ;  although,  at  the  same  time,  it  must  be 


THE   BLOOD   IN   CANCER   SUBJECTS 


263 


observed  that  the  presence  of  the  increased  number  of  monocytes 
shows  that  the  bodily  organism  has  not  given  up  the  fight. 

THE  BLOOD  COUNT  AS  MODIFIED  BY  PROTEIN  ANTIGENS 

When  charts,  based  on  the  study  of  original  cases,  showing 
the  results  of  such  blood  counts  in  about  150  original  cases  under 

TABLE  V — ORIGINAL  CASES 

48  UNSELECTED  CASES  APTER  AN  AVERAGE  PEBIOD  OP  102  DATS  OP  PBOTEIN 
TREATMENT. 


Case  No.  I 

Name 

Nature  of  Case 

No.  of  Days 

j 

Red 
Blood 
Corpus- 
cles 

White 
Blood 
Cor- 
pus- 
cles 

tj 

Mono- 
nuclears 

it 

j 

Large 

Small 

106 
311 

271 
223 

135 
133 
167 
8 
192 
353 
305 
88 
209 
186 
261 
250 

221 

395 
307 
48 
326 
207 
372 
40 
165 
264 
283 
259 
268 
274 
281 
298 
43 
24 
208 
159 
407 
25 
32 
47 
247 
382 
44 

Miss  A... 
Mrs.  A... 
Miss  A... 
Mrs.  B... 
Mrs.  B... 
Mr.  B  ... 
Fr.  B.... 
Mrs.  B... 
MissD.. 
Mrs.  D.  . 
MissD.. 
Mrs.  D.  . 
MissE... 
Mrs.  E... 
Miss  P..  . 
Mr.  F... 
Mrs.  G... 
Mrs.  G.. 
Mrs.  H.  . 
Mrs.  H.  . 
Mr.  H... 
Miss  K.. 
Mr.  K... 
Mrs.  K.  . 
Mrs.  L... 
MissL... 
Mrs.L... 
MissMcG 
Mrs.  M.. 
Sr.  M.... 
Mr.  N... 
Mrs.Q... 
Mr.  R... 
Mrs.  S... 
Mrs.S.    . 
Mr.  S..    . 
Mrs.S.    . 
Mrs.S.    . 
Mrs.  S.    . 
Mrs.  T.  . 
Mr.  V.    . 
Mr.  W.    . 
Mr.  W.   . 
Miss  W   . 
Mr.  W... 
Mrs.  Wn 
Mr.  Wk.. 
Mrs.  D.. 

Thyroid.  .. 

195 

4 

IB 
(i!» 
40 

84 
84 
7:{ 
205 
18 
59 
15 
Jll 

r,n 
90 
52 
144 

65 

61 
68 

111 
75 
9(i 
98 
201 
101 
151 
84 
137 
52 
88 
42 
1!» 
131 
ll:( 
9H 
75 
6< 

2ir 

22< 
119 
62 
6( 
19( 

00 
90 
00 
65 

85 
90 
95 

oo 

85 
90 
85 
90 
80 
00 
00 
85 
85 
95 
SO 

90 
00 
75 

00 
90 
00 
95 
00 
75 
90 
00 
95 
70 
70 
80 
81 
90 
90 

100 
100 
95 

80 

6( 

95 
95 

5,376,000 
5,250,000 
4,480,000 
3,328,000 
4,064,000 
5,600,000 
5,296,000 

5,632,000 
4,370,000 
4,032,000 

4,640,000 
2,848,000 
5,440,000 
5,600,000 
3,976,000 
5,000,000 
4,032,000 
4,032,000 
5,320,000 
4,490,000 
5,440,000 
3,840,000 
5,296,000 
4,928,000 
4,040,000 
4,576,000 
4,524,000 
4,960,000 
4,028,000 
4,784,000 
5,308,000 

3,400,000 
2,168,000 
3,856,000 
4,160,000 
5,450,000 
4,496,000 
4,620,000 
5,664,000 
5,728,000 
4,250,000 
3,440,000 
3,804,000 
5,324,000 
4,444,000 

8,000 

6,700 
10,250 

8,400 
8,100 

6,400 

6,500 
9,620 
7,300 

8,000 
7,700 
9,340 

7,200 
11,300 

7,220 
7,100 

5,720 
6,600 
8,300 
9,200 
7,100 
6,300 

6,400 

7,930 
7,800 
8;330 

7,000 
9,000 
7,600 
10,250 

7,500 
6,700 

61.5 
66.5 
58 
79.3 
80.6 
45.5 
55.6 
67 
55.5 
66 
43 
64.3 
58.5 
77.6 
60 
70 
57 
72 
47.5 
67 
74 
62 
62.5 
68 
50 
62 
52 
55 
49 
52.5 
59.6 
62 
77 
62.5 
84 
68.5 
70 
62 
64 
61.25 
78.5 
77 
68 
73 
77.6 
63.5 
44.3 
54 

20 
19 
13.5 
8.3 
10.6 
35 
20 
16 
24.5 
18 
24.5 
16 
24 
13.6 
20 
14.5 
8.3 
11.6 
24 
13 
13.3 
23 
14 
11 
15 
22.5 
15.6 
20 
19.6 
21.5 
20 
23 
14 
24 
4 
11.5 
11.6 
12 
14 
15.5 
15 
9 
15 
11 
13.3 
15.5 
30.3 
25 

15 
22.5 
23 
10.6 
8.6 
10 
20.3 
16 
18.5 
14 
29 
17.3 
16.5 
5 
18.5 
13 
33.3 
12.6 
25 
18 
11.6 
13 
18.5 
20.5 
35 
14.5 
24.6 
16.5 
26 
24.5 
9.3 
14 
7.5 
12.5 
8.6 
14 
10 
26 
21 
18 
6 
13 
16.5 
15 
6.3 
18.0 
23.5 
16.5 

16.8 

3.5 
2 
4.5 
1.6 
.6 
4 
3.3 
1 
1.5 
2 
3.5 
3.3 
1 
3.6 
.5 
2 
.3 
3.6 
2.5 
1 
1 
2 
5 
.5 
0 
1 
7.6 
8 
5.5 
1.5 
1 
1 
1 
1 
2.6 
6 
2.6 
0 
1 
3.75 
.5 
1 
0.5 

2.6 
2. 
2.3 
4.5 

.5 
.6 
0 
0 
0 
) 
0 
0 
0 
0 
.5 
0 
0 
0 

1 

0 
0 
0 
0 
0 
0 
0 
.5 
0 
0 
0 
0 
.5 
0 
.6 
0 
0 
0 
0 
1.5 
0 
0 
0 
0 
0 
0 
0 
0 

Thyroid 

Thyroid  

C.  of  Uterus  
Tuberculosis 

Diabetes  
Carci.  of  Breast 

Thyroid  
Carci.  of  Breast 

Thyroid  
Carci  of  Breast 

Thyroid  

Carci  of  Breast 

Thyroid      

Thyroid 

C.  of  Uterus  .  .  . 

Thyroid           

C.  of  Intestine  

Thyroid    .  . 

Indigestion 

C.  of  Uterus  
Thyroid 

Thyroid  

Thyroid  
Thyroid  
C.  of  Breast 

"    "  (Esophagus  
"    "  Breast  
Toxaemia  
Endoth.  of  Throat  
Carci.  of  Uterus  
Sarc.  Testicle  
Carci.  of  Breast  
Thyroid  
Carci.  of  Breast 

Thyroid  
C.  Mediastinum  

Thyroid... 
Thyroid  
C.  of  Tongue  
C.  of  Breast 

Rheumatoid  Arthritis.  .  . 

Averai 

;e  

102 

89 

4,673,000 

7,830 

63.4 

16.9 

2.33 

-1 

protein  treatment  were  available,  it  was  at  once  evident  that  there 
were  very  striking  and  characteristic  modifications  of  the  dif- 
ferential count  coincident  with  the  administration  of  the  vege- 
table proteins;  and  that  these  were  curiously  similar  to  changes 
coincident  with  the  administration  of  an  anti-thyroid  serum. 


264  THE   PROTEAL   TREATMENT   OF   CANCER 

A  typical,  yet  somewhat  extreme,  case,  for  example,  was  that 
of  a  patient  suffering  from  carcinoma  of  the  throat  whose  blood 
on  the  8th  of  October,  1915,  at  an  early  stage  of  the  treatment 
showed  7.3  per  cent,  of  large  mononuclears  to  18  per  cent,  of 
small  ones ;  and  whose  count  about  six  weeks  later  (on  the  22nd 
of  November)  was  almost  precisely  reversed  as  regards  these 
particular  elements,  showing  18.3  per  cent,  of  large  mononuclears 
to  7.6  per  cent,  of  small  ones. 

Other  specific  cases  show  the  proportion  between  large  and 
small  mononuclears  as  follows :  19  to  20.6  at  an  early  stage  of 
treatment  and  34  to  11.5  at  a  later  stage;  14  to  31.6  at  an  early 
stage,  and  27.75  to  15  at  a  later  stage;  9  to  16  at  an  early  stage, 
and  21.5  to  8  at  a  later  stage;  and  10.5  to  29  at  an  early  stage, 
against  31  to  15.5  after  three  months  of  treatment. 

A  typical  thyroid  case  showed  the  balance  between  large  and 
small  mononuclears  as  8  to  19.6  on  the  12th  of  October,  and 
shifted  to  25  to  19.5  on  the  17th  of  December,  after  two  months 
of  use  of  anti-thyroid  serum. 

It  seems  a  fair  inference  that,  since  vegetable  proteins  on  one 
hand  and  anti-thyroid  sheep  serum  on  the  other  produce  precisely 
the  same  results  in  human  subjects  that  Vaughan  observed  in 
case  of  the  sheep  inoculated  with  cancer  tissue,  the  principle  in- 
volved is  the  response  to  the  protein  antigen  as  such  rather  than 
a  specific  response  to  any  particular  type  of  protein. 

This,  it  will  be  observed,  would  be  fully  in  keeping  with  the 
assumption  that  the  mononuclear  leucocytes  are  the  agents  chiefly 
involved  in  beginning  the  decompounding  of  foreign  proteins  in 
general  when  brought  in  contact  with  the  blood. 

Be  the  theoretical  explanation  what  it  may,  however,  the  thing 
that  has  peculiar  significance  in  the  present  connection  is  the  ob- 
served fact  that  the  hypodermic  administration  of  proteins  (inde- 
pendent of  any  other  treatment)  has  been  demonstrated  to  bring 
about  a  very  marked  modification  of  the  leucocyte  count,  in  the 
direction  of  the  increase  of  the  large  mononuclears.  Cases  in 
which  no  favorable  modifications  of  this  kind  have  taken  place 
under  Proteal  treatment  have  not  been  observed  to  make  favor- 
able clinical  progress. 

Fairly  typical  of  desired  results  in  case  number  348,  who  on 
the  15th  of  October  (before  beginning  treatment)  had  a  haemo- 
globin index  of  80  per  cent.,  a  red  count  of  3,168,000,  a  white 
count  of  9,880;  with  78.6  poly.,  10.6  large  monocytes  and  8.3 
small  lymphocytes;  and  who  on  the  1st  of  December  showed  a 
haemoglobin  index  of  90  per  cent.,  a  red  count  of  4,944,000,  and 
a  white  count  of  7,500;  with  66.5  per  cent,  poly.,  21  per  cent, 
large  monocytes,  and  10  per  cent,  small  lymphocytes. 


THE   BLOOD   IN    CANCER   SUBJECTS 


265 


TABLE  VI— ORIGINAL  CASES 
BLOOD  COUNT  IN  22  CASES  OF  INOPERABLE  CANCER  BEFORE  TREATMENT 


|  Case  No.  II 

Name 

Nature  of  Case 

H*m- 
* 

Red 
Blood 
Corpus- 
cles 

White 
Blood 
Cor- 
pus- 
cles 

A 

Mono- 
nuclears 

II 

I 

Large 

Small 

369 
888 

3(iO 
315 
309 
381 
313 
354 
359 
322 
371 
332 
317 
318 
3M 
37(3 
301 
318 
287 
399 
371 
317 

Mrs.B... 
Mrs.C.... 
Mr.  D  
Mr.  D  
Dr.  G  
Mra.H.... 
Mrs.  K... 
Mrs.  M  
Mrs.  Me... 
Mr.  N  
MissN.... 
Miss  V  
Miss  W  
Mr.  E  
Mr.  Me.  .  .  . 
Mrs.  T.... 
Mrs.B..  . 
Mr.  E  
Mr.  H  
Mrs.  M  
Mr.  T  
MissW  

Carci.  of  Breast  

Epithe.  of  Jaw.  ....  .  !  . 
Carci.  of  Larynx 

90-95 
90 
90 
90 

100 

4,480,000 
3,976,000 
3,776,000 
4,668,000 
5,056,000 
4,752,000 
4,960,000 
5,064,000 
3,608,000 
3,212,000 
4,456,000 
5,008,000 
4,137,000 
3,168,000 
4,704,000 
4,600,000 
4,200,000 
3,168,000 
3,592,000 
5,120,000 
4,130,000 
4,137,000 

8,220 
9,330 
7,880 
8,350 

7,600 

8,i50 
9,100 

7',906 
8,880 

9,880 
5,250 
8,300 

9,880 
13,500 
9,300 
10,000 

61 
65.6 
51 
79 
75 
80.5 
61.5 
73.3 
63.6 
74 
65 
64 
66.6 
78.6 
74 
70.3 
48 
78.6 
81.6 
75.5 
53.6 
63.6 

14 
14.3 
17.5 
15 
17 
7.6 
23.5 
12.6 
16.3 
9 
15.6 
16 
14.3 
10.6 
15 
12 
18 
10 
7 
15 
15.6 
14.3 

31.6 

17.3 
23.5 
6 
6 
8.6 
14 
13 
18 
17 
16.3 
24 
20.6 
8.3 
11 
15.2 
31 
8.3 
11.3 
8.5 
23.3 
20.6 

2.6 
2.3 
7.75 
0 
2 

;i.3 

1 
1 
2 
0 
3 
0 
.6 
2.3 
0 
2 
0 
2.3 
0 
1 
8.8 
0.6 

.6 
.3 
.25 

.6 
.3 

0 
0.3 
0.6 

Sarc.  Abdomen  

Carci.  of  Breast  

Epithe.  of  Face.."!.'.'.' 
Carci.  of  Breast  

90 
95 
90 
60 
90-95 
85 
85 
80 
90 
85 
80 
80 
80 
95 
85 
85 

"       "  Stomach.  .... 
Epithe.  of  Mouth  
Car.  Gall  Bladder  
Carci.  of  Larynx  
"  Stomach  
Sarc.  of  Testicle  
Carci.  of  Breast 

Sarc.  of  Jaw  
Care,  of  Breast  

Average 

81.9 

4,271,000 

8,840 

67.95 

14.05 

16 

1.69 

.07 

THE  SAME  22  CASES  AFTER  AN  AVERAGE  PERIOD  OF  41  DAYS  OF  PROTEAL  TREATMENT 


4 

£ 

3 

T  '       1 

White 

Mono- 

$ 

I 

Q 

.5 

Hed 
Blood 

Blood 

£>i 

nuclears 

i  8 

^ 

I 

Name 

Nature  of  Case 

•5 
6 
X 

I 

Corpus- 
cles 

Cor- 
pus- 
cles 

1! 

jl 

1 

Large 

Small 

369 

Mrs.  B  .  .  . 

Carci.  of  Breast  

21 

100 

5,724,000 

6,500 

45.3 

32 

18.3 

3 

1.3 

368 

Mrs.C.... 

29 

95 

4,112,000 

8,500 

64.6 

19 

12.3 

3.6 

.3 

360 

Mr.  D  

EP.  of  jaw  .....;.;; 

89 

95 

4,384,000 

6,600 

52.6 

17.3 

20.6 

9 

.3 

345 

Mr.  D  

Card,  of  Larynx...    . 

21 

90 

4,720,000 

7,880 

73 

16.6 

5 

4.6 

0 

309 

Dr.  G  

Sarc.  of  Abdomen  . 

11 

3,412,000 

7,850 

59 

22.5 

16 

2.5 

0 

381 

Mrs.H.... 

Melanoma  

30 

166 

4,500,000 

8,200 

81 

12.5 

5 

1 

.5 

313 

Mrs.  K  

Card,  of  Breast  .  .  . 

80 

100 

5,564,000 

8,000 

60 

19.3 

17.3 

3.3 

0 

354 

Mrs.  M  

7:J 

100 

5,500,000 

7,800 

60 

23 

14 

2 

1 

359 

Mrs.  Me... 

41               Cl                tl 

57 

100 

4,384,000 

7,200 

59 

16.5 

19 

4.5 

.5 

322 

Mr.  N  

Ep.  of  Face  

71 

85 

4,192,000 

7,700 

51.5 

19.5 

26.5 

2.5 

0 

371 

MissN.... 

Carci.  of  Breast  

84 

95 

4,352,000 

8,600 

59.5 

16.5 

21 

8 

0 

332 

Miss  V  

90 

100 

5,656,000 

8,900 

48.5 

27 

20.5 

4 

0 

317 

Miss  W.  .  .  . 

«<               «                « 

88 

85 

4,944,000 

7,330 

56.6 

21 

18.6 

3.6 

.3 

348 

Mr.  E  ... 

"  Stomach  '.  '.  '. 

47 

!)() 

4,944,000 

7,500 

66.5 

21 

10 

2.5 

0 

314 

Mr.  Me...  . 

Ep.  of  Mouth  

81 

85 

4,888,000 

8,650 

68.3 

19.3 

11.6 

.6 

0 

376 

Mrs.  T  

C.  Gall  Bladder  

62 

100 

4,896,000 

9,600 

62 

15.5 

19.5 

2.0 

0 

301 

Mrs.  B  

Card,  of  Larynx  

82 

90 

3,724,000 

7,270 

75 

14 

11 

0 

0 

348 

Mr.  E  

"Stomach... 

48 

90 

4,944,000 

7,500 

66.5 

21 

10 

2.5 

0 

287 

Mr.  H  

Sarc.  of  Testicle  

4 

85 

3,256,000 

8,500 

73 

12.3 

14.0 

0.6 

0 

399 

Mrs.  M...  . 

Carci.  of  Breast  

8 

100 

4,896,000 

9,500 

69.5 

14.5 

13.5 

1.5 

0 

374 

Mr.  T  

Sarc.  of  Jaw  

32 

95 

4,864,000 

8,300 

70.5 

18. 

6. 

5.5 

0 

317 

Miss  W  

Card,  of  Breast  

86 

85 

4,944,000 

7,330 

56 

21 

18.6 

3.3 

0.3 

Average  

40.4 

93.  r 

4,667,000 

8,000 

62.6 

19.06 

14.94 

2.95 

0.2 

Modification  of  the  blood  count  following  the  administration  of  fairly  vigorous  Proteal 
treatment.  Particular  attention  is  called  to  the  notable  increase  in  the  large  mononudears. 
Such  a  modification  is  certainly  one  of  the  most  characteristic,  and  perhaps  the  most  impor- 
tant, of  the  changes  brought  about  by  the  proteal  treatment.  Note  also  the  increase  in 
haemoglobin  and  in  red  corpuscles,  and  the  decrease  in  white  corpuscles  as  a  whole  and  in  the 
percentage  of  polynuclears. 

These  cases  are  grouped  together  simply  because  they  are  cases  in  which  an  original  blood 
count,  made  before  treatment,  was  supplemented  by  a  subsequent  count  after  treatment. 
They  are  otherwise  quite  unselected,  and  are  strictly  comparable  to  the  cases  shown  in  the 
earlier  chart.  The  blood  picture  of  the  treated  cases  shows  wide  departure  from  the  type- 
picture  supplied  by  the  99  untreated  cases. 


266  THE  PROTEAL  TREATMENT  Of  CANCER 

The  average  results  of  fourteen  unselected  cases  under  the 
protein  treatment  are  summarized  thus:  At  the  beginning  of 
treatment  haemoglobin  index  89  per  cent.,  red  corpuscles  4,500,- 
000,  white  blood  corpuscles  8,878 ;  with  68  per  cent,  polymorphs ; 
14.9  'per  cent,  large  monocytes ;  14  per  cent,  small  lymphocytes ; 
.65  per  cent,  eosinophiles ;  and  0.32  basophiles.  At  a  later  stage 
after  an  average  of  42  days  of  protein  treatment,  haemoglobin 
index  96  per  cent.;  red  corpuscles  4,930,000,  and  white  blood 
corpuscles  8,107;  with  62  per  cent,  polymorphs;  18  per  cent, 
large  monocytes ;  and  16  per  cent,  small  lymphocytes ;  3  per  cent, 
eosinophiles ;  and  0.35  basophiles. 

SOME  PRACTICAL  HINTS 

It  is  almost  axiomatic  to  say  that  observation  of  the  blood 
count  must  in  future  be  regarded  as  indispensable  as  a  guide  to 
dosage  and  frequency  of  administration  in  carrying  out  the  pro- 
teal  treatment  of  cancer.  This  is  particularly  true,  however,  after 
treatment  has  been  continued  for  a  period  of  five  or  six  weeks. 

Up  to  that  time,  there  is  almost  certain  to  be  favorable  progress 
of  the  case  if  the  remedy  is  pressed  pretty  actively  from  the  outset, 
the  doses  being  carried  to  the  point  of  securing  a  pronounced  gen- 
eral reaction  on  at  least  one  occasion,  and  subsequently  modified 
so  that  there  is  a  mild  reaction. 

During  this  stage,  there  will  usually  be  observed  a  pronounced 
increase  of  red  blood  corpuscles;  but  this  is  no  more  notable  than 
the  lymphocytosis,  with  marked  preponderance  of  the  large  cells. 

It  should  be  observed,  however,  that  the  activities  of  the  mono- 
cytes in  beginning  the  decompounding  of  cancer  cells  may  be  so 
great  as  to  put  so  severe  a  tax  on  the  energies  of  the  red  blood  cor- 
puscles that  their  numbers  will  be  for  a  time  materially  reduced, 
even  when  the  case  is  progressing  favorably. 

A  very  good  illustration  of  this  is  furnished  by  case  309,  in 
which  there  was  a  large  abdominal  sarcoma  located  near  the  spine, 
which  had  been  declared  irremovable  after  an  exploratory  incision. 
On  the  19th  of  September,  1915,  two  days  after  beginning  the 
Autolysin  treatment,  this  patient  showed  a  red  blood  count  of 
5,066,000 ;  with  75  per  cent,  polymorphs,  17  per  cent,  large  mono- 
cytes ;  6  per  cent,  small  lymphocytes  and  2  per  cent,  eosinophiles. 
Two  weeks  later  the  red  blood  count  had  decreased  3,412,000;  but 
in  the  meantime  the  polynuclears  had  decreased  to  59  per  cent. ; 
there  being  now  22.5  per  cent,  large  monocytes,  16  per  cent,  small 
lymphocytes,  and  2.5  per  cent,  eosinophiles. 

Taken  by  itself,  the  decrease  in  red  blood  corpuscles  might  seem 
alarming;  but  that  the  above  interpretation  of  this  decrease  is 
correct  is  suggested  by  the  fact  that  the  patient  went  ahead  stead- 


THE   BLOOD   IN    CANCER   SUBJECTS  267 

ily  and  rapidly  to  clinical  recovery  with  apparent  entire  regression 
and  disappearance  of  the  tumor,  so  far  as  could  be  determined 
by  palpation.  The  case  was  supposed  to  be  hopeless  by  the  sur- 
geon who  attempted  the  operation;  yet  progress  was  so  spectac- 
ular under  the  protein  treatment  (exclusively)  that  a  few  weeks 
later  the  patient  returned  to  his  home  and  took  up  once  more  his 
accustomed  work  as  a  practising  physician. 

Such  a  reduction  in  the  red  blood  corpuscles  under  the  Proteal 
treatment  as  that  just  noted  would  be  regarded  with  equa- 
nimity, however,  only  where  there  was,  as  in  the  instance  cited,  a 
large  tumor  mass  undergoing  rapid  disintegration.  And  even  then, 
it  is  questionable  whether,  as  a  rule,  it  would  be  desirable  to  carry 
forward  the  disintegration  of  the  tumor  mass  so  rapidly  as  to 
produce  a  marked  reduction  in  the  red  blood  corpuscles.  A  bet- 
ter way,  ordinarily,  would  be  to  regulate  the  dosage  so  as  to 
secure  only  such  amount  of  hydrolysis  of  cancer  cells  as  can  be 
dealt  with  by  the  red  blood  corpuscles  without  reducing  their 
ranks  much  below  the  five-million  mark. 

Cases  are  reported  where  the  dosage  of  proteins  was  pressed 
so  actively  from  the  outset  that  the  breaking  down  of  a  pelvic 
cancer  was  effected  so  rapidly  that  the  system  could  hardly  have 
been  expected  to  withstand  the  shock  had  there  not  been  oppor- 
tunity for  exterior  discharge  and  drainage.  One  physician  de- 
scribed the  results  attained  in  such  a  case  as  reminding  him  of 
the  effects  of  a  curette,  so  rapid  was  the  removal  by  exfoliation 
of  the  cancer  tissue. 

In  such  a  case,  there  is  obvious  danger  of  severe  hemorrhage. 
This  danger  would  be  obviated,  at  least  in  a  measure,  if  the  dosage 
were  so  regulated  that  the  decompounding  of  the  cancer  cells  was 
less  rapid. 

I  have  elsewhere  pointed  out  that  the  critical  period  in  the 
treatment  of  cancer  cases  comes  after  an  interval  of  several 
weeks,  when  the  systemic  response  has  been  carried  to  the  maxi- 
mum. Almost  invariably,  the  question  then  arises  as  to  the  best 
manner  of  continuing  treatment,  in  order  that  the  effects  may  be 
cumulative,  and  the  case  carried  to  the  favorable  termination  that 
seemed  promised  by  the  early  response. 

It  is  now  that  constant  appeal  should  be  made  to  the  microscope 
to  determine  the  precise  status  of  the  red  blood  corpuscles  and 
the  various  leucocytes.  An  endeavor  should  be  made  to  keep  the 
former  as  near  as  possible  to  the  five-million  mark ;  while  it  is  to 
be  hoped  that  the  lymphocytes  will  continue  to  represent  at  least 
one-third  of  the  leucocyte  count,  and  that  the  large  mononuclears 
will  outnumber  the  small  ones. 

A  typical  satisfactory  blood  count  is  shown  by  patient  number 
239  (carcinoma  of  the  breast),  whose  blood  on  the  8th  of  Janu- 


268 


THE  PROTEAL  TREATMENT  OF  CANCER 


ary,  1916,  after  about  six  months'  treatment,  showed  100  per  cent, 
haemoglobin,  5,096,000  red  blood  corpuscles,  and  8,000  leucocytes 
with  60  per  cent,  polys.,  23.5  large  monocytes;  13  per  cent,  small 
lymphocytes;  2.5  eosinophiles,  and  1  per  cent,  basophiles. 

At  the  time  when  this  count  was  made,  the  patient  was  steadily 
progressing,  and  she  went  ahead  to  seemingly  complete  clinical 
recovery. 

TABLE  VII— ORIGINAL  CASES 

THIRTY-ONE  UNSELECTED  CASES  OF  INOPERABLE  CANCER  AT  EARLIER  AND  LATER  STAGES 

OF  PROTEIN  TREATMENT 
FIRST  COUNT  AFTER  AN  AVERAGE  PERIOD  OF  NINETY  DAYS  OF  TREATMENT 


Case  No.  | 

Nature 

Nature  of  Case 

No.  of  Days  | 

I 

Red 
Blood 
Corpus- 
cles 

White 
Blood 
Cor- 
pus- 
cles 

a 

Mono- 
nuclears 

W  a 

Large 

Small 

294 
366 
278 
16 
153 
263 
270 
94 
233 
239 
131 
258 
248 
235 
64 
149 
370 
84 
289 
242 
138 
163 
347 
193 
280 
296 
23 
168 
251 
189 
391 

Dr.  A  
Sr.A  
Mrs.  B.... 
MissD.... 
Mrs.  G.... 
Mrs.  H.... 
Mrs.  H.... 
Mrs.  H.... 
Mrs.  L.  .  .  . 
Mrs.  M  .  .  . 
Mrs.N.... 
Mrs.  N.... 
Mr.O  
Mr.P  
Mr.P  
Mrs.R.... 
Mrs.  R.... 
MissR.... 
Mr».S.... 
Mrs.  S  
Mrs.F.S.. 
Mrs.S.... 
Mrs.  S... 
Mr.S  
Mrs.S.... 
Mr.  Von  E. 
MissW... 
MissW.  .  . 
Mrs.  W.  .  . 
Mr.  M.... 
Mrs.W... 

Ep.  of  Tongue  
C.  of  Breast 

43 
106 

Kir, 

I  li:i 
87 
12G 
5 

96 
95 
90 
90 
88 
90 

4,864,000 
4,448,000 
4,400,000 
4,464,000 
4,656,000 
3,744,000 

7,330 
8,200 

7,500 

74.6 
66 
58.6 
59 
73 
58 
73 
56 
65 
64.3 
62 
59 
71 
68.3 
72 
63.5 
72.6 
71.76 
51.5 
60 
56.3 
65 
42 
63 
74 
64 
60 
6U 

77.6 
52.0 

7.3 
13.5 
19 
17 
13 
20 
17 
26 
19.5 
16.3 
18.6 
18 
9 
14 
9.5 
21 
14 
11.5 
20 
10.6 
17 
20 
28 
19.6 
15.6 
20 
13 
11.6 
11 
11.6 
25.5 

18 
16 
20.6 
24 
12 
20 
9 
14 
15 
15.6 
18.3 
23 
16 
9 
18.5 
15.5 
10.6 
16.25 
25 
29 
24.3 
16 
30 
20 
6.6 
26 
27 
20 
11 
10.6 
14 

0 

3.75 
1.6 
0 
0 
2 
1 
4.5 
.5 
3.6 

0 
.3 
4 
0 
0 
2.6 
.5 
3.5 
.5 
2.3 
0 
0 
1.5 
4 
0 
0 
2 
4 
0.6 
8.0 

;;    Uterus'.'.'.'.'.     ! 
"    Breast 

Ep.  Forehead  
C.  of  Breast  

"    Uterus'.'.'. 
"    Breast  
Sarc.  of  Test  
C.  of  Jaw.  .  . 
Ep.  of  Cheek 

190 
28 
141 
171 
47 
72 
05 
115 
79 
5 
170 
38 
G!) 
129 
21 
90 
165 

ir,!» 

24 
124 

88 
63 

83 
60 

95 

'96 
100 
90 
85 

"so 

86 
95 
95 
90 
75 
85 
75 
76 
100 
100 
90 
80 
80 
85 
80 
100 

5,160,000 

4,680,000 
3,376,000 
5,964,000 
5,330,000 
4,352,000 
4,352,000 
4,240,000 
4,570,000 
4,896,000 
5,128,000 
4,616,000 
2,800,000 
3,654,000 
4,226,000 
4,280,000 
3,936,000 
4,460,000 
4,730,000 
4,440,000 
4,448,000 
3,570,000 
4,312,000 
4,116,000 

8,300 

7,200 
7,600 

10,200 
10,200 

9,000 

8,440 
7,600 
7,200 

8,800 

C.  of  Breast  
"    Skin  
Chond-Sarc  
C.  of  Breast 

Ep.  of  Face  
Sarc.  ofPhar  
C.  of  Breast 

"    Jaw.  .  .' 
"    Thyroid... 

Sarc.  of  Leg  
C.  of  Breast 

"    Rectum'.'.'. 
"    Ovary  

Average  

90 

88.6 

4,400,000 

8,270 

63.69 

16.37 

17.72 

1.7 

This  table  may  advantageously  be  compared  with  earlier  tables  showing  blood  condition 
in  untreated  cancer  cases,  and  with  the  table  on  the  opposite  page,  showing  later  history  of 
the  same  cases. 

It  will  be  of  interest  to  contrast  this  blood  count  with  another, 
No.  399,  which  chanced  to  be  made  on  the  same  day,  in  which 
the  haemoglobin  test  was  also  100  per  cent,  and  in  which  the  red 
blood  count  was  4,896,000,  but  in  which  the  leucocyte  count  was 
9,500  (more  than  could  be  desired),  polymorphs  representing  69.5 
per  cent.,  and  large  monocytes,  only  14.5  per  cent.,  as  against  14.5 
per  cent,  small  lymphocytes,  together  with  1.5  per  cent,  eosino- 
philes and  1  per  cent,  basophiles. 


THE  BLOOD  IN  CANCER  SUBJECTS 


269 


Here,  it  will  be  observed,  there  is  substantial  uniformity  be- 
tween the  two  counts  except  as  regards  three  factors :  namely  ( 1 ) 
the  total  leucocyte  count,  which  was  9,500  in  the  second  patient 
against  8,000  in  the  first ;  (2)  the  polynuclear  count,  which  was 
69.5  against  60;  and  (3)  the  large  monocyte  count  which  was 
14.5  against  23.5.  These  differences,  however,  are  highly  sig- 
nificant, in  view  of  the  studies  of  the  blood  count  above  outlined. 

TABLE  VIII — ORIGINAL  CASES 

THE  SAME  31  UNSELECTED  CASES  AFTER  AN  AVERAGE  OP  152  DAYS  OF 
PROTEIN  TREATMENT 


Case  No. 

Name 

Nature  of  Case 

No.  of  Days 

! 

Red 
Blood 
Corpus- 
cles 

White 
Blood 
Cor- 
pus- 
cles 

4 

Mono- 
nuclears 

ft 

} 

Large 

Small 

294 
366 
278 
16 
153 
263 
270 
94 
233 
239 
131 
258 
248 
235 
64 
149 
370 
84 
289 
242 
138 
163 
347 
193 
280 
296 
23 
168 
251 
189 
391 

Dr.  A... 
Sr.  A  

Ep.  of  Tongue  
C.  of  Breast  

87 
134 
193 
215 
170 
112 
122 

-"'! 

172 
207 
1  50 

i«;2 

91 

1  'JO 

LG9 
67 

L88 

102 

HO 

175 

i74 

!so 

55 
if! 
98 

152 

90  5,288,000 
100  4,160,000 
100  4,832,000 
100  5,252,000 
90  3,840,000 
100  3,424,000 
95  5,696,000 
955,240,000 
1005,652,000 
1005,096,000 
955,124,000 
100  4,800,000 
90  5,404,000 
905,200,000 
903,904,000 
1005,600,000 
904,130,000 
100  4,928,000 
100  5,184,000 
100  4,672,000 
954,640,000 
1004,928,000 
602,326,000 
1004,376,000 
1005,230,000 
100  4,640,000 
1004,960,000 
100  5,650,000 
95  4,288,000 
80  4,072,000 
95  5,632,000 

9,800 
6,700 
6,100 
7,500 
7,500 
7,700 
6,800 
8,000 
8,600 
8,000 
8,300 
9,400 
8,300 
8,880 
11,700 
6,800 
12,000 
10,000 
7,300 
7,200 
8,000 
7,000 
10,500 
6,900 
7,400 
7,800 
9,000 
9,200 
8,600 
7,520 
8,100 

73 
48 
54.5 
61.5 
55 
72.5 
72.5 
58.5 
76.5 
60 
62 
58.5 
71.5 
87.6 
84 
74 
77.5 
57 
61.5 
50.5 
53 
61.5 
40 
60 
72 
60.5 
72 
64.5 
64.5 
69.3 
54 

64.4 

18.3 
26 
34 
13 
22 
10 
17.5 
18 
13.5 
23.5 
20.5 
26.5 
20.5 
7.3 
10.5 
13.5 
15 
13.5 
16 
31 
11 
22.5 
19 
16.5 
18 
20 
16 
18 
19.5 
11.6 
25 

18.3 

7.6 
24.5 
11.5 
24 
20.5 
15.5 
5.5 
21.5 
8.5 
13 
16.0 
13.5 
8 
4.6 
4.5 
9.5 
6.5 
28 
20 
15.5 
32.5 
13 
39 
21 
7 
14.5 
9 
17 
18.6 
18.6 
17.5 

15.6 

2.6 
1.5 
0 
1.5 
2.5 
2 
4 
2 
1 
2.5 
1.5 
1.5 
0 
.3 
1 
8 
1 
1.5 
2.5 
3 
2.5 
2.5 
1 
1.5 
2.5 
1.5 
2.5 
.5 
3.3 
.3 
3.5 

L9 

1 
0 
0 
0 
0 
0 
0 
0 
.5 
1 
0 

0 

0 
0 

0 
0 
0 
0 
0 
0 
.5 
1 
l 
.5 
.5 
.5 
0 
.3 
0 
0 

0.2 

Mrs.  B.... 
MissD.  .. 
Mrs.  G 

Mrs.H.... 
Mrs.  H  
Mrs-H.... 
Mrs.  L.... 
Mrs.  M.... 
Mrs.  N  .  .  . 
Mrs.  N.... 
Mr.  O.  .. 
Mr.  P... 
Mr.  P  
Mrs.  R.  .. 
Mrs.  R.  .  .  . 
MissR.... 
Mrs.  S  
Mrs.  S  
Mrs.  F.  S.  . 
Mn».S  
Mrs.8  
Mr.  S  
Mrs.  S  
Mr.  Von  E  . 
MissW.... 
Miss  W  
Mrs.W.... 
Mr.  M  
Mrs.  W.  .  .  . 

"  "  Breast"  ! 

Ep.  Forehead  
C.  of  Breast  

"  "  Uterus  . 

"  "  Breast  . 

Sarc.  Testicle  
C.  of  Jaw  
Ep.  of  Cheek  
C.  of  Breast  
"  "  Skin  
Chond-Sarc  
C.  of  Breast  
Ep.  of  Face  
Sarc.  of  Phar  
C.  of  Breast  

"  "  Jaw  
"  "Thyroid  
Sarc.  of  Leg  
C   of  Breast 

"    "  Rectum  
"  Ovary  

Average 

95.5 

4,782,000 

8,270 

Comparison  with  the  preceding  table  will  show  characteristic  progress  during  this  period 
of  fourth  and  fifth  months  (on  the  average)  of  Proteal  treatment. 

Nothing  more  would  have  been  necessary  to  make  the  two 
counts  identical  as  to  their  leucocyte  percentage  balance  than  to 
take  the  9.5  per  cent,  in  excess  of  polymorphs  in  the  second  case 
and  transfer  them  to  the  large  monocyte  column.  I  am  greatly 
disposed  to  believe  that  had  the  Proteal  treatment  been  able  to 
effect  such  a  modification  of  blood  count,  there  would  have  been 
a  modification  in  the  production  of  the  leucocytic  enzymes  that 
might  have  turned  the  scale  in  the  patient's  favor.  As  it  was, 
however,  the  second  patient  developed  a  small  metastasis  in  the 
neck  while  undergoing  the  treatment,  which  so  alarmed  her  that 


270  THE   PROTEAL  TREATMENT  OF  CANCER 

she  went  to  another  city  for  X-ray  treatment.  A  few  months 
later  her  death  was  reported. 

What  might  have  been  the  progress  of  the  case  had  the  Proteal 
treatment  been  continued  is  oi  course  only  conjectural.  But 
the  blood  count  showed  that  the  case  was  not  progressing  under 
the  proteals  as  satisfactorily  as  could  be  desired;  whereas  the 
blood  count  of  the  other  patient  gave  every  warrant  for  the  favor- 
able prognosis  that  was  presently  justified. 

Incidentally  we  may  note  that  both  these  cases  were  cancers  of 
the  breast. 

In  another  connection,  I  have  suggested  that  when  a  patient 
under  the  Proteal  treatment  has  been  carried  to  a  stage  of  very 
marked  improvement,  progress  may  be  retarded  by  excessive 
dose,  putting  a  tax  upon  the  corpuscles  that  is  not  compensated 
by  further  stimulus  to  the  blood-forming  organs.  Obviously,  the 
guide  as  to  this  must  be  found  in  the  blood  count. 

In  general,  I  would  suggest  that  when  the  red-cell  count  has 
been  brought  to  approximately  five  millions,  and  the  differential 
leucocyte  count  to  the  status  above  suggested,  in  which  there  is 
marked  lymphocytosis  with  distinct  preponderance  of  the  large 
mononuclears,  the  physician  should  be  chary  of  giving  large  doses 
of  protein. 

It  may  be  desirable  to  discontinue  treatment  altogether  for  a 
time;  but  it  is  usually  preferable  to  restrict  the  size  of  dosage, 
and  extend  the  intervals  between  doses.  A  dose  of  5  or  10 
minims  given  weekly  or  semi-weekly  may  keep  the  corpuscular 
response  at  a  maximum,  and  foster  progress  that  would  be  im- 
possible under  larger  or  more  frequent  doses.  Yet  the  same  case 
may  have  required  dosage  of  40  or  50  minims  daily  or  on  alter- 
nate days  at  an  earlier  stage. 

All  therapeutic  rules  have  exceptions,  however;  so  I  must  add 
that  it  appears  sometimes  to  be  advantageous  to  give  a  patient 
who  has  reached  the  static  period  the  shock  of  a  large  dose,  or 
of  an  intravenous  injection,  which  produces  a  vigorous  reaction. 
A  case  was  recently  reported  in  which,  quite  by  accident,  part 
of  a  dose  was  given  into  a  vein.  There  was  anaphylactic  reac- 
tion within  a  few  minutes,  and  subsequently  the  neoplasm  began 
rapidly  to  regress,  although  it  had  for  some  weeks  been  static, 
after  having  passed  through  an  earlier  stage  of  favorable  progress. 

All  this,  however,  only  emphasizes  the  point  made  in  an  earlier 
section,  to  the  effect  that  any  one  who  can  administer  a  hypo- 
dermic injection  may  begin  the  proteal  treatment  of  a  case  of 
cancer,  and  for  a  time  secure  gratifying  results ;  but  that,  even  in 
cases  that  have  larger  possibilities,  these  possibilities  can  be  rea- 
lized only  when  the  subsequent  administration  of  the  remedy  is 
carried  forward  along  scientific  lines.  One  object  of  the  present 


CANCER  AND  THE  LYMPHOID  SYSTEM  271 

section  has  been  to  suggest  that  the  scientific  administration  in 
question  necessarily  connotes  repeated  observation  of  the  blood 
count  as  modified  by  the  administration  of  the  proteal  antigens. 


SECTION  IX. 
CANCER  AND  THE  LYMPHOID  SYSTEM 

There  is  one  profoundly  important  aspect  of  the  problem  of 
treating  cancer  with  proteins  to  which  incidental  reference  has 
been  made  in  this  monograph,  but  which,  so  far  as  I  am  aware, 
has  never  been  elsewhere  suggested. 

The  point  in  question  is  this:  Every  cancer  patient  has  been 
subjected  to  a  spontaneous  course  of  protein  treatment  before  he 
comes  into  the  hands  of  the  surgeon  or  physician. 

Such,  at  least,  must  be  considered  the  fact  if  the  thesis  as  to 
the  nature  of  cancer  that  furnishes  the  basis  of  this  monograph 
is  accepted.  According  to  that  thesis,  as  elsewhere  elaborated, 
there  is  incessant  warfare  from  the  outset  between  the  blood  cor- 
puscles and  the  neoplastic  cells,  with  the  consequent  destruction 
of  combatants  on  both  sides. 

If  the  corpuscles  win,  the  lawless  cells  are  entirely  eliminated, 
and  no  tangible  neoplasm  will  result. 

But  if  the  new  cells  win,  they  ultimately  constitute  an  aggre- 
gate that  we  call  a  tangible  cancer.  Meantime,  there  has  been 
an  effort  on  the  part  of  the  bodily  defenders — namely,  the  white 
and  red  corpuscles — that  has  profoundly  disturbed  their  status 
as  health-defending  agents.  And  needless  to  say  this  profound 
disturbance  has  extended  to  the  organs  that  produce  the  blood 
corpuscles,— namely  the  bone  marrow,  the  lymphatic  system,  and 
the  spleen.  Abundant  proof  of  this  is  found  in  the  presence  of 
myelocytes,  normoblasts,  and  abnormal  lymphoid  corpuscles  in  the 
blood  stream. 

The  manner  of  change  that  brings  about  this  modification  of  the 
blood  conditions  may  be  illustrated  by  a  quotation  from  Dr. 
Ward's  book  on  Bedside  Hamatology.  In  the  chapter  on  "Gen- 
eralized Affections  of  Blood-forming  Tissues"— in  which  there  is 
no  specific  reference  to  cancer — he  says: 

"It  is  well  known  that  the  most  powerful  and  efficient  stimu- 
lants of  blood  regeneration  are  the  products  of  blood  destruction. 
This  is  well  shown  in  the  case  of  Addisonian  [pernicious]  anaemia 
and  in  the  results  of  injections  of  very  small  quantities  of  blood 
in  cases  of  anaemia.  We  need  not  then  be  surprised  if  after  this 
destruction  we  find  excessive  formation.  We  do,  as  a  matter  of 
fact,  find  both  excessive  formation  of  white  cells  and  the  pres- 


272  THE  PROTEAL  TREATMENT  OF  CANCER 

ence  of  the  products  of  excessive  destruction  in  the  urine.  The 
next  step  in  the  pathology  will  be  the  reversion  of  the  cell- forming 
organs  to  a  more  primitive  type  as  a  result  of  the  continued  strain 
on  them.  This  also  we  find  in  lymphsemia  as  we  do  in  Addisonian 
anaemia.  Here,  however,  the  analogy  ends  for  the  reversion  in 
the  case  of  lymphsemia  may  proceed  in  the  extent  of  resurrecting 
tissues  whose  cell-forming  days  were  over." 

Elsewhere  in  the  same  chapter,  the  salient  aspect  of  the  sub- 
ject is  elaborated  as  follows : 

"In  the  group  of  diseases  now  to  be  discussed  the  common  and 
distinctive  feature  is  involvement  of  all  the  blood-forming  or- 
gans by  a  growth  or  overgrowth  that  is  similar  in  each  organ. 

"In  the  first  sub-group,  the  leukaemias,  not  only  the  adult  blood- 
forming  organs,  marrow,  spleen,  and  lymph  glands  are  effected 
but  in  other  situations  tumors  may  appear  which  are  composed 
of  tissue  identical  with  that  in  the  marrow,  etc.  These  tissues 
are  the  embryonic  and  infantile  blood-forming  organs,  the  liver 
and  thymus,  .and,  secondly,  connective  tissue  wherever  met  with. 
This  extraordinarily  wide  distribution  of  lesions  in  some  cases  is 
the  more  readily  explained  when  we  remember  that  all  mesoblastic 
tissue  is  potentially  Wood-forming — i.e.,  blood-cell-forming — just 
as  it  is  potentially  sarcomatous  or  fibromatous." 

To  understand  the  subsequent  sequence  of  events,  we  have  to 
recall  that  overstimulation  of  any  organ  leads  presently  to  ex- 
haustion. So  the  same  stimulus  that  at  first  produces  an  excess 
of  blood  corpuscles  may  presently  result  in  marked  decrease.  Note, 
for  example,  what  Pappenheim  says  as  to  this: 

"Leucopenia  is  not  diametrically  opposed  to  hyperleucocytosis 
even  when  it  appears  from  the  first  as  a  leucopenia,  e.g.,  in  typhoid. 
It  ought  rather  to  be  regarded  as  differing  in  degree  only,  since 
high  degrees  of  leucocytosis,  or  leucocytosis  of  long  standing,  may 
merge  into  leucopenia.  When  this  occurs,  especially  if  accom- 
panied by  the  presence  of  early  forms  [leucoblasts,  myelocytes, 
normoblasts]  in  the  blood,  it  indicates  commencing  exhaustion  of 
the  overtaxed  bone  marrow." 

Such  are  the  recognized  effects  of  a  persistent  stimulation  of 
the  organs  of  blood  regeneration  by  the  products  of  blood  de- 
struction. It  must  be  obvious,  then,  that  in  every  far-advanced 
case  of  cancer,  or  at  any  rate  in  every  case  in  which  a  neoplasm 
has  assumed  considerable  proportions,  there  must  be  a  greater  or 
less  degree  of  what  Ward  refers  to  as  "hyperprophy  of  the  lym- 
phocyte-forming tissues,"  including  spleen  and  marrow.  Ac- 
cording to  the  present  thesis,  the  increased  formation  of  lympho- 
cytes and  early  myelogenous  forms  in  response  to  the  stimulus  of 
the  cancer  cells  is  a  salutary  process, — an  attempt  on  the  part  of 
the  organism  at  spontaneous  cure  of  the  malady.  But  the  net 
result,  when  the  new  growth  is  too  active,  is  that  ultimately  the 
organs  of  blood- formation  have  reached  their  maximum  response 


CANCER  AND  THE  LYMPHOID  SYSTEM  273 

to  that  particular  antigen,  and  through  prolonged  overstimulation 
a  general  myelogenous  and  lymphatic  maladjustment  is  produced 
which  is  in  many  respects  comparable  to  the  general  leukaemias 
of  different  origin.  "Many  people,"  says  Ward,  "consider  that 
leukaemia  is  of  the  nature  of  a  malignant  growth  as,  for  instance, 
cancer  of  the  stomach  is  a  malignant  growth."  Again  he  says: 
"That  there  are  analogies  between  cancer  and  the  leukaemias  no 
one  will  deny."  He  adds  that  in  his  opinion  these  analogies  are 
not  sufficient  to  bring  the  two  into  the  same  class ;  admitting  at  the 
same  time  that  theories  in  the  matter  are  at  present  only  tentative, 
and  going  on  to  say  that:  "If  leukaemias  are  cancer,  then  the 
metastases  of  cancer  are  not  due  to  emboli  from  a  primary  growth 
nor  to  spread  by  direct  continuity  along  lymphatics,  but  are  pri- 
marily formed  in  each  situation  in  which  they  occur  under  the 
influence  of  the  same  stimulus  that  produced  the  original  tumor." 
To  be  sure,  Ward  thinks  that  most  pathologists  will  not  subscribe 
to  this  view  of  cancer  metastases,  and  so  will  reject  the  analogy 
which  suggests  that  leukaemia  is  to  be  regarded  as  a  form  of  new 
growth  of  the  bone  marrow  or  glands.  He  adds,  however,  that 
"the  theory  and  the  analogy  form  a  fascinating  and  possibly  pro- 
ductive field  for  discussion  and  research." 

There  is  no  occasion  here  to  enter  into  detailed  discussion  of 
the  pathological  questions  involved.  My  object  in  referring  to 
it  is  to  emphasize  the  view  that  the  presence  of  a  cancerous 
growth  implies  a  profound  dyscrasia  of  the  lymphoid  tissues. 
There  is  of  course  nothing  new  in  this  view,  although  it  may  per- 
haps be  said  that  there  is  novelty  in  the  explanation  of  the  fact 
just  offered, — the  suggestion,  namely,  that  the  lymphatic  hyper- 
trophy may  be  a  direct  result  of  the  response  to  the  antigenic 
stimulus  of  the  decompounding  cancer  cells. 

From  a  practical  standpoint,  the  importance  of  the  matter  lies 
in  the  fact  that  a  full  recognition  of  the  conditions  will  prevent 
anyone  from  supposing  that  he  has  effectively  treated  a  case  of 
cancer  when  he  has  merely  removed  a  local  neoplasm. 

More  specifically,  the  matter  is  important  in  the  present  con- 
nection as  emphasizing  the  view  that  a  cancer  patient,  before  he 
comes  into  the  hands  of  the  physician,  has  undergone  a  radical 
course  of  protein  treatment.  This  fact  is  immensely  significant 
in  its  bearing  on  the  practicalities  of  a  subsequent  course  of  pro- 
tein treatment  at  the  hands  of  the  physician. 

If  the  view  just  presented  is  accepted,  for  example,  it  becomes 
obvious  that  any  further  treatment  based  on  the  administration 
of  cancer  proteins  (and  such  treatment  has  been  suggested  and 
extensively  tested)  would  be  illogical  in  the  highest  degree.  All 
that  cancer  proteins  can  accomplish  as  antigens  has  already  been 
accomplished,  and  the  net  result  is  that  the  patient  still  has  a 


274  THE  PROTEAL  TREATMENT  OF  CANCER 

neoplasm  associated  with  a  responsive  dyscrasia  of  the  blood- 
forming  organs.  Hence  the  futility  of  the  autolysate  treatment 
of  Fichera  and  allied  attempts  to  treat  cancee  with  so-called" 
"vaccines"  made  from  the  tissue  of  neoplasms. 

A  disturbance  of  the  blood  count,  or  a  deviation  from  the  nor- 
mal, in  token  of  cytogenic  dyscrasia,  may  be  expected  as  a  matter 
of  course.  If  the  neoplasm  is  small,  as  in  case  of  a  epithelioma 
of  the  mouth,  the  antigenic  stimulus  of  the  cancer  cells  may  be  of 
so  relatively  slight  a  character  that  the  blood  picture,  at  the  time 
when  the  patient  comes  under  observation,  may  be  identical  with 
that  which  has  been  presented  in  an  earlier  chapter  as  typically 
favorable.  The  red  blood  count  may  be  above  five  million ;  the 
white  count  about  8,000;  and  the  mononuclears  may  constitute 
35  or  40  per  cent  of  the  leucocytes  with  a  preponderance  of  large 
monocytes;  and  there  may  be  relatively  high  percentage  of  eos- 
inophiles. 

This  would  indicate,  according  to  the  present  thesis,  that  the 
patient  in  question  is  receiving  spontaneous  protein  treatment  that 
is  accomplishing  valuable  results  in  retarding  the  progress  of  the 
malady. 

More  commonly,  however,  as  records  of  our  counts  have  shown, 
the  patient  at  the  time  of  first  examination  has  reached  a  stage 
at  which  the  corpuscular  balance  is  much  less  favorable.  The 
stimulus  to  the  cytogenic  apparatus  (in  particular  the  bone  mar- 
row), followed  by  exhaustion,  is  revealed  in  a  relative  monocy- 
penia,  but  with  marked  preponderance  of  the  small  lymphocytes, 
associated  with  a  deficiency  of  eosinophiles,  and,  usually,  with  a 
marked  decrease  of  the  red  corpuscles.  Commonly  there  is  marked 
general  leucocytosis,  but  with  preponderance  of  the  polynuclears. 
Myelocytes,  leucoblasts,  and  normoblasts  may  be  present  in 
greater  or  less  profusion.  The  poly  nuclear  commonly  show 
marked  deviations  from  the  normal  as  regards  the  conformation 
of  the  nucleus  (S-shaped  nucleus,  ring-form,  spiral  contortion, 
etc.),  with  in  general  a  marked  tendency  toward  "progression  to 
the  left," — speaking  in  terms  of  the  Arneth  formula. 

This  pciture  suggests  that  a  spontaneous  cancer-antigen  treat- 
ment has  passed  its  maximum  of  efficiency,  and  that  relatively 
rapid  and  unfavorable  progress  of  the  neoplasm  must  now  be 
expected  unless  a  new  and  different  stimulus  can  be  brought  to 
bear  on  the  defensive  mechanism  of  the  body. 

Such  a  new  stimulus  may  be  supplied  by  the  X-ray,  by  radium, 
or  by  the  administration  of  proteins  of  a  type  quite  different  from 
the  proteins  of  cancer. 

In  discussing  the  action  of  X-ray  and  radium  elsewhere  I  have 
suggested  that  the  beneficial  effect  of  these  rays  may  be  in  part 
at  least  due  to  their  general  influence  on  the  blood  count.  I  wish 


CANCER  AND  THE  LYMPHOID  SYSTEM  275 

now  to  emphasize  this  aspect  of  the  matter  in  the  light  of  the 
statement  above  quoted  from  Ward  to  the  effect  that :  "It  is  well 
known  that  the  most  powerful  and  efficient  stimulants  of  blood 
regeneration  are  the  products  of  blood  destruction." 

I  am  inclined  to  think  that  a  large  measure  of  the  benefits 
sometimes  unquestionably  attained  in  cancer  from  the  use  of  X- 
ray  and  radium  may  be  explained  as  due  to  their  destructive  in- 
fluence on  the  blood  corpuscles.  It  is  well  known  that  in  general 
leukaemias,  the  number  of  white  corpuscles  may  be  reduced  by 
X-ray  treatment.  It  is  also  known  that  radium  exercises  a  de- 
structive influence  on  the  blood  corpuscles.  It  follows  that  these 
influences  must  stimulate  the  blood-forming  mechanism,  inasmuch 
as  their  use  tends  to  saturate  the  blood,  more  or  less,  with  "the 
products  of  blood  destruction." 

In  point  of  fact,  I  have  observed  that  patients  that  had  un- 
dergone X-ray  or  radium  treatment  before  applying  for  Proteal 
treatment  sometimes  show  a  blood  picture  precisely  of  the 
kind  that  we  have  come  to  regard  as  favorable,  and  as  indicating 
the  best  possible  response  to  the  proteal  treatment  itself.  I  am 
strongly  inclined  to  the  opinion  that  in  many  cases  this  favorable 
blood  picture  is  directly  due  to  the  use  of  X-ray  or  radium,  and 
that  the  beneficial  effects  of  these  treatments  are  in  a  large  meas- 
ure due  to  this  general  modification  of  the  blood  quite  as  much  as 
to  any  local  effect  on  the  neoplasm. 

Indeed  I  think  it  is  an  open  question  whether  it  may  not  be 
possible  to  get  the  good  effects  of  X-ray  or  radium  by  treatment 
applied  generally,  or  to  the  bones  or  to  the  spleen,  rather  than 
by  prolonged  application  to  the  site  of  the  neoplasm  itself.  This, 
however,  is  a  matter  that  need  not  be  discussed  in  detail  in  the 
present  connection.  It  suffices  to  emphasize  the  opinion  that  pro- 
longed exposure  to  X-ray  or  radium  at  the  site  of  the  neoplasm 
is  inadvisable ;  and  that  the  danger  of  local  burns,  with  their 
characteristically  disagreeable  and  resistent  ulcers,  may  be  obvi- 
ated without  sacrificing  any  of  the  expected  benefits,  by  shifting 
the  locus  of  treatment. 

Incidentally,  it  may  be  noted  as  a  matter  of  interest  that  radium, 
when  introduced  into  the  animal  organism,  is  believed  to  have 
something  like  an  elective  affinity  for  the  bone  marrow,  taking 
permanent  lodgment  there.  So,  at  least,  I  have  been  informed 
by  one  of  the  most  experienced  workers  in  this  field,  who  stated 
this  as  a  matter  of  fact,  quite  without  reference  to  any  theory  as 
to  the  action  of  radium  on  the  blood-forming  mechanism. 

It  is  the  commonly  accepted  opinion  of  pathologists  that,  where- 
as the  X-ray  exerts  a  temporarily  beneficial  effect  in  the  treatment 
of  leukaemias,  the  effects  cease  to  be  cumulative  after  a  time,  and 
ultimately  the  beneficial  response  ceases,  and  the  patient  goes 


276  THE  PROTEAL  TREATMENT  OF  CANCER 

on  to  a  period  of  decline,  which  the  X-ray  now  seems  powerless 
to  retard. 

We  must  expect,  I  think,  that  the  same  thing  will  ordinarily  be 
true  of  the  X-ray  or  radium  treatment  of  the  type  of  lymphaemia 
or  myelaemia  associated  with  the  presence  of  malignant  neoplasms. 
It  was  above  suggested  that  the  neoplasm  assumes  significant  pro- 
portions only  when  the  blood-forming  mechanism  has  ceased  to 
respond  effectively  to  the  antigenic  stimulus  of  the  "cancer  pro- 
teins. When  this  has  occurred,  a  new  stimulus  may  be  given  to 
the  blood-forming  apparatus  by  X-ray  or  radium  treatment.  In 
a  certain  number  of  cases,  this  new  stimulus  may  be  sufficient  to 
turn  the  scale  in  favor  of  the  bodily  defenders,  and  against  the 
neoplasm ;  with  the  result  that  the  lawless  cells  are  totally  disinte- 
grated, and  a  condition  of  at  least  clinical  cure  is  effected.  But 
in  a  much  larger  proportion  of  cases,  it  cannot  be  hoped  that  the 
new  stimulus  given  by  the  radiation  treatment  will  serve  to  turn 
the  tide  so  effectively.  In  a  vast  preponderance  of  cases,  the  neo- 
plasm will  be  found  to  be  so  thoroughly  fortified  that  it  offers  suc- 
cessful resistence  to  the  best  fighting  equipment  that  the  body 
can  develop  under  the  new  stimulus. 

Even  where  the  local  neoplasm  seems  completely  to  disappear 
under  the  new  stimulus,  it  is  a  matter  of  unfortunate  observation 
that  either  direct  or  metastatic  recurrences  presently  reveal  them- 
selves, showing  that  the  profound  lymphatic  dyscrasia,  however 
modified,  has  not  been  eliminated. 

In  such  a  case  (and  this  is  equivalent  to  saying,  in  practically 
all  cases  of  cancer),  it  is  desirable  to  seek  still  other  methods  of 
stimulating  the  cytogenic  apparatus,  and  thus  further  to  fortify 
the  fighting  equipment  of  the  body.  The  therapeutic  agents  avail- 
able for  this  purpose  include:  (1)  Hygienic  measures,  such  as 
proper  food,  exercise,  massage,  and  cold  baths;  and  (2)  An  in- 
definite series  of  foreign  proteins,  animal,  bacterial,  and  vegetable. 


SECTION  X. 

ANIMAL  EXPERIMENTATION  AND  PROTEAL 
THERAPY 

About  the  year  1908  workers  at  the  Loomis  Laboratory 
were  experimenting  with  transplantable  tumors  in  dogs.  They 
found  that  with  dogs,  as  with  rats  and  mice,  some  individuals 
seemed  immune  to  the  transplantation  of  such  tumors.  In 
other  cases,  the  tumor  after  transplantation  grows  for  a  time 
and  then  "spontaneously1'  regresses.  In  yet  others,  it  continues 
to  grow  until  it  brings  about  the  death  of  the  animal.  As  with 


ANIMAL  EXPERIMENTATION  AND  PROTEAL  THERAPY          277 

rats  and  mice,  the  dog  that  had  recovered  through  "spontaneous" 
regression  of  a  tumor  appeared  to  be  immune  to  subsequent 
transplantation. 

It  occurred  to  the  experimenters  to  test  the  effect  of  transfusing 
the  blood  of  such  an  immunized  animal  into  the  vascular  system 
of  a  dog  in  which  the  transplanted  tumor  was  progressing. 
Experiments  were  first  made  with  the  blood  serum  of  the  im- 
munized dog;  and  the  results  were  negative.  But  when,  subse- 
quently, transfusion  was  made  of  the  whole  blood  of  the  dog,  a 
curative  result  was  abserved,  the  tumor  in  the  affected  animal 
regressing,  and  the  dog  going  on  to  complete  recovery. 

It  seemed  fairly  obvious,  then,  that  there  was  something  in  the 
entire  blood  of  the  animal  that  was  not  conveyed  with  the  serum 
alone  that  served  as  an  antagonist  to  the  cancer  cell.  It  is  re- 
called that  on  one  occasion  a  not  unnatural  suggestion  was  made 
by  a  visiting  physician  who  had  witnessed  the  results  of  these 
experiments  to  the  effect  that  possibly  this  curative  principle 
might  reside  in  the  bodies  of  the  leucocytes.  The  suggestion  was 
recognized  as  having  interest  and  plausibility,  but  the  trend  of 
thought  at  the  moment  was  in  the  direction  of  chemical  explana- 
tions of  a  less  tangible  kind,  and  no  immediate  attempt  was  made 
to  verify  or  refute  the  leucocytic  hypothesis.  The  matter  came 
naturally  to  mind,  however,  when  several  years  later,  observation 
was  made  of  the  modification  of  blood  count  under  influence  of 
the  protein  treatment  of  human  cancer  subjects. 

When  the  series  of  blood  counts  made  in  my  experimental 
laboratory  had  reached  the  stage  at  which  it  became  evident 
that  there  were  highly  interesting  modifications  of  the  leucocyte 
count  (specifically  characterized  by  an  increase  of  mononuclear 
leucocytes,  and  in  particular  of  the  large  mononuclears),  it 
became  a  matter  of  interest  to  examine  the  literature  of  experi- 
mentation in  quest  of  records  of  analogous  experiences. 

Then  it  became  apparent  that  there  is  a  peculiar  paucity  of 
observations  on  the  differential  count  of  the  white  corpuscles  in 
an  otherwise  expansive  literature ;  due,  no  doubt,  to  the  fact  that 
most  workers  have  been  concerned  with  the  biochemical  rather 
than  the  histological  aspects  of  the  investigation.  It  was,  I  think, 
the  late  Elbert  Hubbard— voicing  a  familiar  conclusion— who 
made  the  cogent  observation  that,  in  matters  of  science,  we 
appear  always  to  progress  from  the  complex  to  the  simple,  and 
that  the  obvious  is  the  last  thing  to  be  observed.  Experiments 
in  cancer  inoculation  with  animals  would  seem  to  furnish  another 
illustration  of  the  truth  of  this  observation,  inasmuch  as  very 
tangible  and  obvious  modifications  of  the  blood  count  have  for  the 
most  part  been  overlooked  by  workers  who  were  concerning 
themselves  with  intricate  problems  of  bodily  metabolism  involv- 


278  THE  PROTEAL  TREATMENT  OF  CANCER 

ing  chemical  conditions  susceptible  of  investigation  only  by  the 
most  delicate  of  biological  methods. 

Fortunately,  however,  there  are  a  few  workers  who  appear  to 
have  been  impressed  with  the  histological  aspects  of  the  problem, 
although  even  these  have  for  the  most  part  considered  this  aspect 
of  the  subject  as  having  only  subordinate  interest. 

Among  the  earliest  and  most  important  observations  that  asso- 
ciate the  leucocytes  with  the  process  of  immunization  of  animals 
against  cancer  inoculation  are  those  of  Bashford,  Murray  and 
Cramer,  working  under  the  auspices  of  the  Imperial  Cancer 
Research  Fund,  in  England.  In  a  report  published  in  the  Pro- 
ceedings of  the  Royal  Society  of  London  for  1909,  dealing  with 
the  general  subject  of  resistant  cancer  inoculation,  in  mice,  they 
make  the  following  highly  interesting  observations: 

"The  phagocytosis  of  formed  cellular  elements  plays  an  im- 
portant role  in  inducing  resistance;  serum  is  impotent  to  induce 
resistance,  blood  corpuscles  do  so.  The  energetic  phagocytosis 
which  accompanies  the  spontaneous  absorption  of  transplanted 
tumors,  and  which  occurs  in  absorption  after  exposure  to  radium, 
speaks  strongly  for  the  conclusion  that  the  processes  are  the  same 
in  kind  when  blood  or  tumor  cells,  being  absorbed,  produce 
resistence.  But  we  are  as  yet  unable  to  determine  the  extent  to 
which  agencies  directed  against  the  tumor  cells  themselves  may 
assist  in  determining  their  early  death  in  protected  animals." 

At  an  earlier  stage  of  the  series  of  investigation,  the  role  of 
the  leucocyte  had  been  under  consideration,  as  shown  by  a  report 
made  by  Bashford,  Murray,  and  Bowen,  in  the  Proceedings  of 
the  Royal  Society  for  1906.  In  this  report  the  authors  say : 

"Of  course  the  cells  presenting  complete  degeneration  are  no 
longer  capable  of  giving  rise  to  tumors.  In  fact  they  are  rapidly 
taken  up  by  the  phagocytes  in  the  days  immediately  preceding 
transplantation,  and  it  might  be  concluded  that  growth  was  con- 
tinued by  cells  which  never  tended  to  degenerate." 

Incidentally  it  is  of  interest  to  note  that  in  connection  with  this 
report  the  authors  show  a  drawing  of  inoculated  tumor  tissues 
undergoing  degeneration,  in  which  portions  of  the  mass  that  stain 
lightly  are  surrounded  'by  cells  with  dark-staining  nucleus  and 
protoplasm  of  a  type  closely  similar  to  cells  that  I  have  observed 
and  studied  in  detail  in  a  patient's  blood  taken  from  the  im- 
mediate substance  of  a  cancerous  mass. 

In  continuance  of  the  same  line  of  observation,  we  find  Da 
Fano  in  the  Fifth  Scientific  Report  of  the  Imperial  Cancer 
Research  Fund,  issued  in  1912,  referring  to  the  round  cells  that 
occur  in  the  margin  of  a  tumor  that  is  retrograding,  and  along 
the  strands  of  actively  proliferating  connective  tissue.  De  Fano 
suggests  that  the  development  of  tumor  immunity  in  mice  is 
coincident  with  the  general  reaction  of  the  connective  tissue 
throughout  the  organism.  He  observed  that  the  polynuclear  leu- 


ANIMAL  EXPERIMENTATION  AND  PROTEAL  THERAPY          279 

cocytes  appear  first  at  the  place  of  the  implanted  tumor,  and 
undergo  degeneration,  without  showing  phagocytic  activity.  The 
lymphocytes  then  appear  in  large  numbers  in  the  region  of  the 
inoculated  tumor,  gradually  diminishing  after  immunity  is  estab- 
lished. According  to  his  observation,  inoculation  of  dead  tumor 
cells  was  not  followed  by  round  cell  infiltration  nor  by  the  de- 
velopment of  tumor  immunity.  The  observations  were  thought 
to  establish  a  close  relationship  between  the  leucocytosis  and  the 
development  of  tumor  immunity. 

Dr.  F.  W.  Baeslack,  of  Detroit,  Mich.,  was  led  to  take  up  a 
specific  investigation  of  the  modifications  of  the  leucocytic  blood 
count  in  mice  suffering  from  transplanted  tumors.  The  results  of 
his  researches  were  published  in  the  Zeitschrift  fiir  Immunitats- 
forschung  for  1913.  He  points  out  that  the  observation  of  the 
increase  of  leucocytes  in  cancer  was  made  as  long  ago  as  1843 
by  Andrae,  and  confirmed  in  detail  by  Liidke  in  1867.  The  latter 
observer  concluded  "that  the  increase  in  the  number  of  leucocytes 
was  a  sign  that  the  disease  had  become  general  and  involved  the 
whole  body."  Reference  is  made  to  other  workers  who  have 
made  observations  on  the  leucocytes  in  cancer,  but  the  list  is  a 
surprisingly  short  one  considering  the  enormous  bulk  of  cancer 
literature  in  general. 

Dr.  Baeslack's  experiments  had  to  do  with  several  series  of 
inoculated  cancer  mice.  He  states  that  his  count  of  the  blood 
Icells  included  the  large  mononuclears  and  the  eosinophiles,  but 
his  percentages  and  charts  are  given  only  for  polynuclears  and 
small  lymphocytes.  As  to  these  he  says: 

"It  is  of  interest  to  note  that  the  small  mononuclear  lympho- 
cytes decreased  during  the  period  of  active  tumor  growth,  while 
the  polymorphonuclear  leucocytes  increased,  and  that  shortly  be- 
fore the  retrogression  of  the  tumor  became  noticeable  the  rela- 
tionship between  these  two  classes  of  cells  was  entirely  changed." 

The  charts  presented  give  graphic  illustration  of  the  observa- 
tion that  when  the  polynuclear  leucocytes  went  up  and  the  small 
lymphocytes  went  down,  the  case  was  progressing  badly.  In 
one  case  at  an  early  stage  the  polynuclears  went  up  to  55  per 
cent,  and  the  lymphocytes  went  down  to  26  per  cent.  (It  must 
be  recalled  that  the  polynuclears  are  relatively  sparse — 16.9  per 
cent.,  according  to  Price  Jones — and  lymphocytes  relatively 
abundant — 59.7  per  cent. — in  normal  mouse-blood).  But  at  a 
later  stage,  when  the  tumor  was  undergoing  regression,  the 
polynuclears  went  down  to  16  per  cent,  (substantially  normal), 
and  the  small  lymphocytes  advanced  to  48  per  cent,  of  the  total 
leucocyte  count,  a  number  probably  within  the  limits  of  normal 
variation. 


280  THE  PROTEAL  TREATMENT  OF  CANCER 

It  is  unfortunate  that  details  are  not  given  as  to  the  remaining 
types  of  leucocytes,  but  it  is  obvious  that  a  simple  computation 
shows  that  at  the  earlier  stage  of  this  experiment,  when  the  tumor 
was  seemingly  overmastering  the  system,  the  large  mononuclears 
and  the  eosinophiles  together  aggregated  only  19  per  cent,  of  the 
leucocyte  count;  whereas  at  a  later  stage,  when  the  tumor  was 
spontaneously  regressing,  the  large  monocytes  and  the  eosino- 
philes together  must  have  aggregated  36  per  cent,  of  the  total 
count,  a  number  far  in  excess  of  the  normal,  which,  according 
to  Price  Jones,  is  represented  by  21.5  per  cent,  of  large  mononu- 
clears and  0.14  of  eosinophiles. 

These  observations  of  general  lymphocytosis  in  cases  of  mouse 
tumors  that  are  progressing  to  recovery  have  obvious  interest  as 
supplementing  the  observations  of  Da  Fano  to  the  effect  that 
lymphocytes  appeared  in  great  numbers  about  inoculations  of 
immunizing  material  during  the  evolution  of  resistance,  and  that 
in  growing  carcinomata  the  presence  of  the  lymphocytes  in  great 
numbers  was  clearly  associated  with  a  local  healing. 

Further  association  between  the  corpuscles  and  the  processes 
of  immunization  was  suggested  by  the  observations  of  Lambert 
and  Haynes  that  rat  sarcoma  would  grow  in  the  plasma  of  immu- 
nized mice  quite  as  vigorously  as  in  that  from  normal  or  tumor- 
bearing  animals, — an  observation  that  obviously  links  with  the 
observations  on  the  curative  properties  of  entire  blood  versus 
serum,  as  recorded  at  the  beginning  of  this  chapter. 

From  the  present  standpoint  these  observations  as  a  whole  have 
quite  exceptional  interest  because  they  reveal  modifications  of  the 
leucocyte  count  in  mice  in  which  tumors  are  undergoing  regres- 
sion that  are  singularly  comparable  to  the  records  of  the  favorable 
case  of  human  cancer  under  protein  treatment  observed  by  me 
and  recorded  in  great  detail  before  I  had  so  much  as  heard  of  Dr. 
Baeslack's  experiments.  It  will  be  recalled  that  charts  were  pre- 
sented to  illustrate  graphically  the  fact  that  in  cases  that  pro- 
gressed most  favorably  under  -Proteal  treatment  the  polynuclears 
and  the  small  lymphocytes  tended  to  approach  the  normal  in 
numbers,  whereas  the  large  monocytes  increased  very  markedly 
and  held  at  high  level. 

It  would  appear  that  the  same  formula  could  be  applied  to  Dr. 
Baeslack's  convalescing  mice;  although  -the  observer  himself  ob- 
viously failed  to  appreciate  the  significance  of  the  large  monocyte 
count,  his  attention  being  fixed  solely  on  the  polynuclears  and 
small  lymphocytes.  Possibly  he  had  overlooked,  or  was  not  aw-are 
of,  the  normal  balance  of  leucocytes  in  mice  (which,  as  just  noted, 
is  very  different  from  that  of  the  human  subject),  and  hence  did 
not  realize  that  the  fall  of  polynuclears  to  about  16  per  cent,  and 
the  rise  of  lymphocytes  to  about  50  per  cent.,  represented  only 


ANIMAL  EXPERIMENTATION  AND  PROTEAL  THERAPY          281 

approximations  to  the  normal ;  whereas  the  really  significant  fea- 
ture of  this  count  had  to  do  with  the  large  monocytes,  which  rose 
far  above  normal  as  the  case  progressed  favorably  (as  we  learn 
by  subtracting  the  polymorphs  and  lymphocytes  from  the  total 
count),  yet  which  he  did  not  think  it  worth  while  specifically  to 
enumerate. 

This  correspondence  between  clinical  experience  with  the 
human  subject  and  laboratory  observation  of  mice,  as  regards  the 
modifications  of  leucocyte  differential  count  when  the  system  ap- 
pears to  be  getting  the  better  of  a  cancer  invasion,  is  at  least 
highly  suggestive. 

That  Price  Jones  should  have  noted  a  rise  of  large  monocytes 
in  cancerous  mice  presumably  not  progressing  favorably  is  ob- 
viously consistent  with  the  thesis  concerning  the  response  to  the 
presence  of  cancer  cells  exposited  in  detail  in  an  earlier  chapter 
of  the  present  work ;  and  it  may  be  observed  that  the  mice  in  ques- 
tion, as  studied  by  Price  Jones,  showed  increase  in  polynuclears 
also,  precisely  as  did  Baeslack's  mice  that  were  not  recovering. 

Of  course  it  will  not  be  overlooked  that  rise  of  polynuclears, 
taken  by  itself,  is  a  phenomenon  familiarly  associated  with  bac- 
terial infections,  and  that  the  latter  may  occur  as  a  complication 
in  many  cases  of  malignant  involvement.  But  it  will  be  obvious 
that  the  modification  of  the  differential  count  recorded  in  the 
protein-response  tables  is  quite  different  from  that  induced  by 
bacterial  infection,  inasmuch  as  a  characteristic  feature  is  the 
reduction  rather  than  the  increase  of  both  relative  and  absolute 
polynuclear  numbers. 

Meantime  it  should  be  observed  that  students  of  the  infections 
have  tended  to  focus  attention  on  the  polynuclear  "microphages" 
to  the  neglect  of  the  mononuclear  "macrophages."  Even  where 
the  latter  were  counted,  the  possible  significance  of  modifications 
of  their  numbers,  is  frequently  overlooked  or  ignored.  Thus  in 
the  very  interesting  and  important  studies  of  Gay  and  Claypole, 
as  recorded  in  the  Archives  of  Internal  Medicine  for  November, 
1914,  in  which  the  leucocytosis  induced  in  normal  and  immunized 
rabbits  by  the  injection  of  Bacillus  typhosus  is  studied  differen- 
tially, stress  is  laid  entirely  on  the  increase  in  polynuclears,  al- 
though the  facts  recorded  permit  interesting  inferences  regarding 
the  large  mononuclears  also,  since  the  actual  count  of  these  cells 
twenty-four  hours  after  inoculation  showed  an  increase  per  cubic 
millimeter  from  670  to  3,014 — a  four-and-a-half-fold  advance. 
It  is  true  that  the  advance  of  polynuclears  was  even  more  over- 
whelming (from  5,226  to  60,480)  ;  but  on  the  other  hand,  the 
small  lymphocytes  advanced  only  from  7,370  to  11,340,  an  in- 
crease of  but  54  per  cent,  suggesting  by  contrast  that  the  four- 
and-a-half  fold  advance  of  the  large  lymphocytes  is  not  to  be 


282  THE  PROTEAL  TREATMENT  OF  CANCER 

explained  as  a  mere  incidental  result  of  general  excitation  of  the 
blood-forming  mechanism. 

It  is  noteworthy  in  this  connection  that  German  clinicians  (for 
example  Von  Domarus)  cite  an  increase  of  large  mononu clears 
as  a  typical  feature  of  the  secondary  stage  of  a  so-called  "leu- 
cocyte-curve" of  infections,  such  increase  following  the  primary 
advance  and  recedence  of  the  polynuclears,  and  preceding  the 
advance  of  the  small  lymphocytes.  Conceivably  this  macrocytosis 
is  to  provide  for  the  hydrolysis  of  the  protein  products  with  which 
the  blood  has  been  flooded  by  the  disintegration  of  the  micro- 
phages  (polynuclears)  with  their  increment  of  partially  digested 
bacteria.  Such  at  any  rate,  might  be  a  plausible  explanation  of 
the  later  aspects  of  the  "leucocyte  curve"  if  the  proteomorphic 
thesis  as  -to  the  proteolytic  activities  of  large  and  small  lympho- 
cytes is  accepted. 

In  general,  it  would  appear  that  a  relative  monocytosis  be- 
tokens a  non-bacterial  protein  invasion  as  clearly  as  a  neutrophile 
increase  betokens  a  bacterial  infection.  Probably  the  diagnostic 
value  of  the  monocytosis  is  not  less  than  that  of  the  polyneu- 
closis,  although  hitherto  quite  unrecognized. 

Further  pursuance  of  the  subject  here,  however,  would  carry 
us  too  far  afield  from  the  present  theme,  which  concerns  malig- 
nant neoplasms  rather  than  general  infections.  Let  us  again 
take  up  the  analysis  of  the  results  of  animal  experimentation  in 
the  cancer  field,  with  an  eye  to  the  correlation  of  these  results 
with  our  own  clinical  and  laboratory  experience  with  cancer  in 
the  human  subject. 

CART  BEFORE  HORSE 

In  considering  various  of  the  observations  above  cited,  and 
numerous  others  in  the  literature  of  transplantable  tumors  in  rats 
and  mice,  one  is  led  to  reflect  on  the  power  of  preconception  and 
the  difference  that  may  result  from  a  changed  point  of  view. 

If  a  person  who  had  seen  automobiles  moving  about  the  streets, 
but  who  now  for  the  first  time  saw  a  horse  and  carriage,  were  to 
describe  what  he  had  seen,  he  would  doubtless  tell  of  an  auto- 
mobile that  pushed  before  it  a  strange  animal.  He  might  even 
note  with  amusement  that  the  animal  was  obliged  to  move  very 
rapidly  to  keep  ahead  of  the  vehicle  that  tends  to  overrun  it. 
Probably  he  would  be  led  to  query  why  it  would  not  be  more  con- 
venient to  tie  the  animal  behind  the  vehicle  and  thus  avoid  the 
danger  of  injuring  it. 

Now  such  a  description  of  the  locomotion  of  the  horse-drawn 
vehicle  would,  in  my  opinion,  be  strictly  comparable  to  the  descrip- 
tions that  have  appeared  in  the  literature  of  cancer  in  connection 
with  the  question  of  the  transplantation  of  tumors  and  the  giving 


ANIMAL  EXPERIMENTATION  AND  PROTEAL  THERAPY          283 

of  immunization.  As  a  case  in  point,  note  the  comment  of  a  very 
industrious  and  laborious  compiler,  reviewing  the  literature  of  the 
subject,  when  referring  to  the  experiments  of  De  Fano,  above 
noted,  as  follows : 

"As  lymphocytes  appeared  in  great  numbers  about  inoculations 
of  immunizing  material  during  the  evolution  of  resistance,  their 
relation  to  this  condition  could  not  be  denied.  ...  In  growing 
carcinomata  they  were  to  be  found  only  in  places  where  local 
healing  was  in  progress.  A  carcinoma  cell  seemed  to  exert  some 
sort  of  specific  influence  on  the  lymphocyte,  and  the  latter  to 
spread  the  resistant  state  throughout  the  organism." 

In  the  light  of  the  interpretation  of  the  action  of  the  lympho- 
cytes that  furnishes  the  chief  thesis  of  the  present  monograph, 
which  will  be  elaborated  presently,  such  a  phrasing  seems  not  less 
ridiculous  than  the  suggestion  that  the  horse  is  pushed  before  the 
carriage. 

To  say  that  lymphocytes  "were  found  only  in  places  where 
local  healing  was  in  progress"  is  a  little  as  if  one  were  to  note 
the  curious  coincidence  that,  in  a  certain  house,  rats  were  to  be 
found  only  in  places  where  cheese  was  disappearing. 

Scarcely  less  absurd  seems  the  interpretation  that  has  been  put 
upon  the  widely  heralded  experiments  of  Ehrlich,  as  repeated  by 
others,  in  what  has  come  to  be  known  as  the  zigzag  transplanta- 
tion of  tumors.  It  will  be  recalled  that  in  this  experiment  a  tumor 
from  a  mouse  is  transplanted  to  the  body  of  a  rat,  where  it  grows 
for  a  time,  and  then  begins  to  undergo  regression.  Before  it  has 
entirely  regressed,  it  is  taken  from  the  body  of  the  rat  and  trans- 
ferred to  the  original  host,  where  it  again  takes  on  more  or  less 
energetic  growth.  It  will  be  recalled  that  Ehrlich  explained  this 
with  an  elaborate  theory  of  so-called  atrepsia,  according  to  which 
there  are  certain  chemical  constituents  in  the  organism  of  the 
mouse  that  are  essential  to  the  growth  of  the  mouse  tumor;  that 
a  certain  quantity  of  this  material  is  transferred  with  the  tumor 
to  the  body  of  the  rat,  and  that  when  this  transferred  portion  is 
exhausted,  the  growth  can  no  longer  continue  in  the  body  of  the 
rat. 

In  the  light  of  the  present  thesis,  the  explanation  of  zigzag 
transplantation  would  be  simply  that  the  transplanted  tumor  grew 
for  a  short  time  in  the  body  of  the  rat  because  a  certain  time  was 
required  to  muster  the  companies  of  corpuscles  to  combat  the  law- 
less cells.  When  the  corpuscular  defenders  had  been  aggregated 
in  sufficient  numbers,  the  fight  with  the  cancer  cells  would  turn 
in  favor  of  the  host,  and  the  cancer  would  begin  to  regress.  Now, 
however,  the  remainder  of  the  cancer  cells  are  retransferred  to  the 
mouse,  where,  as  a  matter  of  course,  they  continue  to  grow  be- 
cause it  had  already  been  demonstrated  that  the  body  of  that  par- 
ticular mouse  was  not  competent  to  produce  corpuscles  and  their 


284  THE  PROTEAL  TREATMENT  OF  CANCER 

enzymes  in  sufficient  quantity  to  combat  the  activities  of  the  cancer 
cells. 

A  similar  explanation,  obviously,  may  be  found  for  the  ob- 
served fact  that  an  animal  may  be  rendered  immune  to  inocula- 
tion experiments  not  merely  by  inoculation  with  the  cancer  tissue, 
but  with  tissues  of  various  kinds,  including  heteromorphous  ones. 
For  example,  Dr.  Isaac  Levin  reported  the  immunization  of  rats 
by  treatment  with  mouse  tissue.  (Proceedings  of  the  Society  for 
Experimental  Biology  and -Medicine,  1910.)  Other  experimenters 
have  produced  immunization  with  the  tissues  of  liver,  spleen,  and 
other  organs.  The  evidence  seems  to  justify  the  expectation  that 
immunity  may  be  developed  by  the  introduction  of  various  protein 
substance,  whether  derived  from  the  tissues  of  animals  of  the 
same  species,  or  of  other  species.  In  a  word,  it  would  appear 
that  we  have  to  do  with  a  general  protein  reaction.  Couple  these 
observations  with  the  observations  of  Bashford  and  his  associates 
and  of  Baeslack,  and  we  might  fairly  expect — were  not  our  minds 
turned  in  the  opposite  direction — that  an  essential  modification 
of  the  leucocyte  count  would  be  found  in  all  of  these  cases ;  and 
we  might  justify  the  inference  that  such  modification  had  an  im- 
portant relation  to  the  process  of  immunization. 

When,  now,  we  turn  to  the  human  subject,  and  study  the  modi- 
fications of  the  blood  count  in  cancer  cases,  and  in  particular  can- 
cer cases  under  protein  treatment,  as  reported  in  the  present  mono- 
graph, it  is  obvious  how  all  these  observations  of  the  animal  ex- 
perimenters harmonize  with  the  results  shown  in  our  charts ;  and 
the  conclusion  seems  inescapable  that  we  have  to  do  with  a  gen- 
eral principle  of  protein  reaction,  and  with  a  response  of  the 
blood-forming  organs  one  prominent  feature  of  which  is  an  in- 
crease in  the  phagocytic  or  enzymic  activities  of  the  corpuscles. 
This,  after  all,  is  only  giving  specific  application,  in  terms  of  the 
proteomorphic  theory,  to  the  general  conclusion  stated  by  Levin 
in  the  paper  above  cited  on  the  immunization  of  rats  with  mouse 
tissue,  to  the  effect  that:  "The  explanation  must  be  sought  in 
some  protective  substance  within  the  host  created  under  the 
influence  of  the  implanted  mouse  tissue." 

PHAGOCYTIC  ACTIVITIES 

Before  going  on  to  a  more  detailed  exposition  of  what  I  con- 
ceive to  be  the  character  and  manner  of  action  of  this  "protective 
substance,"  I  would  introduce  a  quotation  from  Starling's  stand- 
ard work  on  Physiology  to  remind  the  reader  of  the  really  ex- 
traordinary part  that  phagocytic  activities  play  in  physiological 
processes. 

"We  have  seen,"  says  Starling,  "that  the  leucocytes  from  what- 
ever animal  they  may  be  taken  present  two  phenomena,  viz.,  that  of 


ANIMAL  EXPERIMENTATION  AND  PROTEAL  THERAPY  285 

amoeboid  movement  and  that  of  ingesting  foreign  particles  which 
may  be  presented  to  them.  On  account  of  this  power  of  eating 
up  foreign  particles  they  are  frequently  spoken  of  as  'phagocytes,' 
in  this  respect  resembling  unicellular  organisms  and  the  undif- 
ferentiated  cells  of  many  kinds  of  tissue.  All  the  phenomena  con- 
nected with  the  process  of  inflammation  in  higher  animals  are 
directed  to  the  assemblage  of  leucocytes  at  the  spot  which  is  the 
seat  of  injury  or  of  infection,  so  that  they  may  devour  and  remove 
either  the  injured  tissue  or  the  invading  micro-organisms.  This 
process  plays  therefore  an  important  part  in  determining  the  im- 
munity of  any  animal  against  infection;  though  in  the  higher 
animals  it  is  assisted  by  a  number  of  other  mechanisms  directed 
towards  the  same  e"nd,  which  we  shall  have  to  discuss  in  a  subse- 
quent chapter.  The  use  of  phagocytosis  is  not,  however,  confined 
to  the  protection  of  the  organism  against  infection.  Wherever 
any  effete  or  dead  tissue  has  to  be  cleared  away,  whether  as  the 
result  of  injury  or  in  the  course  of  metamorphosis  of  organs,  the 
leucocytes  play  an  important  part.  Thus  in  the  great  rearrange- 
ment of  tissues  which  occurs  in  the  larval  state  of  insects,  the  re- 
moval of  the  muscle  fibres  which  are  no  longer  required  is  effected 
by  the  accumulation  of  phagocytes  around  them.  The  phago- 
cytes may  send  processes  into  the  muscle  substance,  which  dis- 
solve this  tissue  and  then  take  it  up.  The  absorption  of  the  tail 
of  the  tadpole  is  effected  in  the  same  way  by  means  of  phagocytes. 
In  mammals,  including  man,  the  moulding  of  the  long  bone  which 
occurs  in  the  process  of  growth  is  effected  by  continual  and  coin- 
cident processes  of  absorption  and  new  formation  of  bone.  The 
absorption  is  carried  out  by  means  of  spinal  phagocytes  formed  by 
the  aggregation  of  a  number  of  leucocytes,  the  well-known  'giant 
cells'  or  myeloplaxes  which  form  so  prominent  a  constituent  of 
bone-marrow. 

"The  blood-corpuscles  represent  the  wandering  phagocytes  of 
the  body.  There  are  fixed  phagocytes  of  which  the  myeloplaxes 
just  mentioned  may  be  regarded  as  a  type.  Other  members  of 
this  class  are  the  endothelial  cells  (Kupfer's  'Sternzellen')  which 
line  the  capillaries  of  the  liver.  If  a  suspension  of  carmine  or  of 
micro-organisms  be  injected  into  the  blood  stream  these  endo- 
thelial cells  are  found  a  little  later  to  have  taken  up  large  numbers 
of  the  foreign  bodies.  Under  normal  circumstances  these  cells 
as  well  as  some  similar  cells  in  the  spleen  take  up  effete  red  blood- 
corpuscles  and  destroy  them.  During  the  process  of  ^degeneration 
of  a  peripheral  nerve  brought  about  by  its  separation  from  the 
ganglion-cells  of  which  its  fibres  are  the  processes,  a  marked  pro- 
liferation of  the  nerve-nuclei  takes  place.  These  become  sur- 
rounded with  protoplasm  and  act  the  part  of  phagocytes,  loading 
themselves  with  the  fat  globules  set  free  by  the  degeneration  of 
the  myelin  sheath.  To  the  same  class  of  fixed  phagocytes  may 
possibly  be  ascribed  certain  of  the  plasma-cells  of  the  connective 
tissues. 

"That  the  polymorphonuclear  leucocytes  are  endowed  with 
these  phagocytic  properties  is  universally  acknowledged,  but  some 


286  THE  PROTEAL  TREATMENT  OF  CANCER 

doubt  still  exists  as  to  how  far  the  other  types  of  leucocytes  which 
we  have  described  can  function  as  phagocytes.  It  is  probable  that 
the  lymphocytes,  and  certainly  the  large  mononuclear  or  hyaline 
corpuscles,  are  endowed  with  these  properties.  The  granular  cor- 
puscles, namely,  eosinophile  and  basophile,  are  thought  by  some 
to  function  as  unicellular  glands  and  to  react  to  infection,  not  by 
englobing  the  micro-organisms,  but  by  discharging  substances 
stored  up  in  their  granules  which  have  a  poisonous  effect  on  the 
micro-organisms,  and  so  prepare  them  for  subsequent  ingestion 
by  the  polymorphonuclear  leucocytes." 

A  very  striking  illustration  of  the  phagocytic  activities  of  leuco- 
cytes is  given  in  certain  abnormal  conditions,  notably  in  so-called 
phagocytic  anaemia.  This  condition  is  characterized  by  active 
phagocytosis  of  blood  cells  by  other  blood  cells  of  normal  or  ab- 
normal type  in  the  circulating  blood.  Ward  says  of  this :  "The 
resulting  blood  picture  is  very  striking.  In  one  case  the  phago- 
cytosis was  so  pronounced  that  it  was  calculated  that  if  all  the 
cells  were  as  actively  phagocytic  as  one  which  was  observed  ac- 
tually in  perfect  cells  on  the  warm  stage,  the  whole  of  the  red 
cells  of  the  body  would  have  been  destroyed  in  less  than  two 
hours.  In  this  case  the  destruction  produced  a  fatal  anaemia. 
Other  cases  have  followed  transfusion  or  have  been  associated 
with  some  known  haemolytic  process  such  as  cholaemia.  Isolated 
phagocytic  cells  may  be  met  with  in  malaria  and  leukaemia  and 
no  doubt  in  other  diseases." 

The  active  share  that  the  large  mononuclear  leucocyte  takes  in 
this  process  is  noted  by  Ward  and  graphically  depicted  in  a  draw- 
ing showing  large  mononuclear  phagocytes,  "Many  of  them  con- 
taining several  cells  or  portions  of  cells  which  have  been  caught." 
One  of  these  mononuclear  phagocytes  appears  to  have  engulfed 
no  fewer  than  seven  red  corpuscles.  Another  has  engulfed  two 
large  cells  that  have  the  appearance  of  polynuclears.  The  picture 
gives  graphic  support  to  the  nomenclature  of  Metchnikoff,  who 
designated  the  polynuclears  as  microphages  and  the  large  mon- 
onuclears  as  macrophages. 

These  activities  of  phagocytes  may  be  recalled  in  connection 
with  the  observations  already  cited  of  similar  functioning  in  the 
removal  of  the  detritus  of  cancer  cells,  as  noted  by  Bash  ford  and 
his  associates.  It  may  be  noted  also  that  Walker,  in  dealing  with 
the  effect  of  certain  serums  on  carcinoma  in  mice,  observes  that 
if  pieces  of  tumor  are  placed  in  the  serum  of  a  rat  which  has  been 
injected  with  extract  of  mouse  testis,  degeneration  of  the  cancer 
cell  takes  place,  the  cells  being  invaded  and  replaced  by  leuco- 
cytes. It  does  not  appear  that  this  observation  has  been  verified 
by  other  workers,  'but  it  has  obvious  interest  in  connection  with 
the  not  dissimilar  observations  of  the  other  workers  already  cited. 
In  particular,  note  the  observation  of  Bash  ford,  Murray,  and 


ANIMAL  EXPERIMENTATION  AND  PROTEAL  THERAPY          287 

Cramer  as  to  the  "energetic  phagocytosis  which  accompanies  spon- 
taneous absorption  of  transplanted  tumors,  and  which  occurs  in 
absorption  after  exposure  to  radium,"  and  the  observation  of  two 
of  the  same  workers  that  cancer  cells  presenting  complete  degen- 
eration "are  rapidly  taken  up  by  phagocytes  in  the  days  imme- 
diately succeeding  transplantation." 

All  in  all,  it  would  appear  that  there  is  abundant  warrant  for 
the  assumption  that  the  leucocytes  have  an  important  share  in  the 
attempt  of  the  organism  to  combat  the  invasion  of  cancer  cells. 
Probably  the  evidence  justifies  the  belief  that  they  have  the  im- 
portant share,  though  the  co-operation  of  the  red  corpuscles  is 
so  essential  (according  to  the  present  thesis)  that  these  agents 
can  scarcely  be  said  to  be  subordinate. 

If  this  conclusion  is  justified,  it  would  seem  to  follow  as  a  mat- 
ter of  course  that  a  medicinal  agent  to  combat  cancer  should  be 
sought  along  the  lines  of  a  stimulus  to  the  blood-forming  organs. 
It  does  not  appear,  however,  that  any  one  definitely  formulated 
such  an  idea  until  an  agent  clinically  observed  to  benefit  the  cancer 
subject  was  found  to  have  acted  through  stimulation  of  the  blood 
count — in  particular  increasing  the  numbers  of  red  corpuscles  and 
large  mononuclears. 

TYPES  OF  LEUCOCYTES 

It  will  have  been  observed  that  throughout  the  foregoing  dis- 
cussion we  have  been  concerned  with  concrete  and  tangible  facts. 
Let  us  supplement  these  facts  by  recalling  the  series  of  tables  in 
which  it  was  demonstrated  that  the  administration  of  vegetable 
proteins  brings  about,  in  the  average  cancer  case,  a  conspicuous 
and  progressive  increase  of  the  large  mononuclear  leucocytes, 
which  were  seen  to  advance  from  the  normal  maximum  of  four 
or  five  per  cent,  of  the  leucocyte  count  to  15  per  cent.,  18  per  cent., 
19  per  cent.,  and  25  per  cent.,  on  the  average,  in  successive  groups 
of  cases ;  reaching  a  much  higher  figure  in  individual  cases. 

With  these  series  of  facts  for  background,  it  will  not  be  with- 
out interest  to  make  inquiry  as  to  the  manner  of  action  through 
which  the  increased  armies  of  large  monocytes  exercise  their  an- 
tagonistic influence  against  cancer  cells,  and  thus  benefit  the 
patient. 

At  the  outset  I  would  suggest  the  advisability  of  not  drawing 
too  sharp  a  line  of  distinction  between  the  two  types  of  mononu- 
clear leucocytes,  namely,  the  small  lymphocytes  and  large  mono- 
cytes. It  must  be  recalled  that  there  are  still  differences  of  opin- 
ion as  to  the  origin  of  the  large  monocytes,  some  physiologists 
contending  that  they  are  merely  overgrown  lymphocytes.  A  more 
popular  view,  probably,  is  that  they  are  of  bone-marrow  origin, 


288  THE  PROTEAL  TREATMENT  OF  CANCER 

and  the  progenitors  of  the  polymorphonuclear  leucocytes.  But 
whichever  view  is  correct,  it  is  scarcely  in  question  that  the  mon- 
onuclear  leucocytes  represent  a  somewhat  more  primitive  type  of 
cell  than  the  polynuclear.  The  polymorphs,  eosinophiles,  and 
basophiles  are  of  granular  structure,  and  it  is  held  that  the  gran- 
ules have  a  secretory  function,  generating  enzymes  that  escape 
into  the  blood  plasma.  In  keeping  with  this  function,  these  cells 
have  in  general  a  relatively  large  cytoplasm,  and  their  nuclear 
structure,  although  elaborated  and  differentiated  in  form,  is  rela- 
tively sparse,  particularly  in  case  of  the  fully  developed  poly- 
morph. 

Meantime,  the  typical  lymphocyte  is  almost  exclusively  com- 
posed of  nuclear  structure ;  and  the  typical  large  monocyte  has  a 
relatively  enormous  nucleus  and  a  relatively  small  amount  of  cyto- 
plasm, as  contrasted  with  the  typical  polynuclear  cell.  There  is, 
however,  a  type  of  large  mononuclear  with  nucleus  less  basic  in 
stain  than  the  typical  large  monocyte,  and  with  full  clear  cyto- 
plasm, which  my  personal  studies  lead  me  to  associate  with  the 
cancer-cell  destroying  process,  and  which  I  am  disposed  to  regard 
as  of  lymphoid  origin — in  effect  an  overgrown  lymphocyte.  Fuller 
discussion  of  the  status  of  this  and  other  types  of  large  mononu- 
clears  is  reserved  for  a  later  chapter. 

In  substantiation  of  the  idea  that  the  mononuclears  are  of  a 
somewhat  more  primitive  type  than  the  polynuclears,  we  find  the 
former  relatively  abundant  in  lower  animals — for  instance,  the 
rabbit,  with  60  per  cent,  of  mononuclears ;  and  the  mouse,  as  al- 
ready cited,  with  80  per  cent,  or  more  of  mononuclear  cells,  one- 
fourth  of  them  large  monocytes,  and  17  per  cent,  of  polynuclears, 
contrasted  with  the  70  per  cent,  of  the  latter  in  the  human  subject. 

Witness  also  the  fact  that  children  show  a  relatively  high  per- 
centage of  mononuclears,  at  once  evidencing  the  primitive  char- 
acter of  these  cells,  and  suggesting  that  they  in  some  way  func- 
tionate in  connection  with  the  control  of  rapidly  growing  tissues. 
In  the  first  and  second  years  of  childhood,  according  to  Von 
Domarus,  the  polynuclears  represent  only  about  42  per  cent,  of 
the  total  leucocyte  count,  the  small  lymphocyte  representing  47 
per  cent.,  the  large  monocyte  (including  transitionals)  about  8 
per  cent.,  and  the  eosinophiles  about  3  per  cent.  By  the  fifteenth 
year,  the  polynuclears  have  risen  to  more  than  56  per  cent.,  and 
the  lymphocytes  have  dropped  to  about  28  per  cent.,  but  the  large 
monocytes  and  transitionals  are  slightly  more  abundant  than  in 
infancy,  representing  about  9  per  cent,  of  the  leucocyte  count, 
while  the  eosinophiles  have  risen  to  not  far  from  6  per  cent.  Be- 
tween puberty  and  adult  life  there  are  further  changes,  result- 
ing ultimately  in  giving  the  polynuclears  a  census  not  far  from 
three-quarters  of  the  total  leucocyte  count;  the  lymphocytes  being 


ANIMAL  EXPERIMENTATION  AND  PROTEAL  THERAPY          289 

about  one-third  as  numerous,  and  the  large  monocytes  dropping 
to  relative  obscurity  with  a  count  of  from  two  to  four  per  cent. 

It  would  appear,  then,  that  the  physiological  conditions  in  the 
body  of  the  normal  mouse  call  for  about  five  times  as  many  large 
monocytes,  proportionately,  as  are  required  in  the  body  of  an 
adult  human  being;  and  that  the  normal  human  being  during 
childhood  and  adolescence  requires  about  twice  as  many  mono- 
cytes as  are  subsequently  called  for. 

Note  now  the  suggestive  fact  that,  according  to  the  observations 
of  Cramer  and  Pringle,  the  tissue  of  a  cancer  (in  mice)  is  of  an 
embryonic  type,  as  shown  by  the  fact  that  its  cells  contain  only 
about  seventy  per  cent,  of  the  nitrogen  content  of  the  average 
tissues  of  the  host.  Cramer  had  indicated  the  similarity  between 
the  growth  of  cancer  and  the  growth  of  the  foetus,  and  prelim- 
inary experiments  by  Dr.  Lochstad  had  shown  that  a  rapidly 
growing  tissue  (foetus)  has  a  lower  nitrogen  value  than  the  ma- 
ternal organism.  These  experiments  obviously  confirm  the  old 
idea  that  cancer  tissue  is  of  somewhat  embryonic  character,  and. 
suggest  the  possibility  that  chemical  or  other  agents  might  be 
found  that  would  serve  to  decompound  the  cancer  cells  without 
injuring  the  normal  surrounding  tissue. 


NATURAL  IMMUNITY  AND  ARTIFICIAL  IMMUNIZATION 

Consider  now  for  a  moment  the  attitude — if  the  word  be  per- 
mitted— of  the  normal  organism  toward  intruding  cancer  cells. 
Here  the  evidence  must  come  largely  from  the  field  of  animal  ex- 
perimentation, but  it  offers  suggestive  hints  that  may  be  applied, 
with  due  reserve,  to  the  human  subject. 

It  is  familiarly  known  that  the  pioneer  work  of  Hameu  and 
Morau,  expanded  a  little  later  by  the  work  of  Jensen  and  Leo 
Loeb,  made  possible  a  new  era  of  investigation  by  showing  that 
carcinomas  and  sarcomas  of  white  mice  and  rats  could  be  trans- 
planted into  other  animals  of  the  same  species.  It  is  equally  well 
known  that  all  experimenters  are  agreed  that  a  certain  number 
of  individual  animals  show  resistance  to  such  transplantation, 
tumors  embedded  in  their  tissues  regressing  and  disappearing 
"spontaneously"  instead  of  continuing  their  lawless  growth. 

Thus  it  is  shown,  as  Dr.  Isaac  Levin  has  phrased  it,  that  "the 
growth  of  the  implanted  tumor  depends  upon  the  correlation  be- 
tween the  virulence  of  the  implanted  cell  and  the  resisting  power 
of  the  organism  of  the  host." 

It  was  further  shown  that  an  artificial  tumor  used  for  inocula- 
tion appears  to  acquire  increasing  virulence  as  it  is  passed  from 
one  animal  to  another.  But,  on  the  other  hand,  it  is  possible  to 
induce  a  condition  in  the  body  of  an  animal  which  at  first  is  sus- 


290  THE  PROTEAL  TREATMENT  OF  CANCER 

ceptible  that  will  render  it  immune  to  further  transplantation. 
This  was  done  by  Ehrlich  and  his  associates  by  making  an  orig- 
inal inoculation  with  a  tumor  known  to  possess  a  low  degree  of 
virulence.  Such  a  tumor  being  absorbed  "spontaneously,"  it  was 
observed  that  the  animal  in  which  such  spontaneous  absorption 
had  occurred  was  now  immune  against  inoculation  with  tumors 
of  a  more  virulent  type  which  would  almost  certainly  have  grown 
had  not  the  animal  been  given  added  powers  of  resistance  by  the 
original  inoculation. 

What  is  of  peculiar  importance  from  the  present  standpoint  is 
the  fact  that  it  was  shown  presently  that  inoculation  with  normal 
tissue,  such  as  liver,  spleen,  and  blood  produced  a  degree  of  im- 
munity comparable  to  that  produced  by  the  inoculation  with  a 
mild  type  of  cancer  cell.  And  most  interesting  of  all  is  the  ob- 
servation of  Dr.  Levin  and  others  that  identical  results  as  to  in- 
duced immunity  may  be  brought  about  by  inoculation  with  so- 
called  autolyzed  tissue,  that  is  to  say,  with  tissue  "of  which  the 
cells  are  killed  in  such  a  manner  as  to  leave  the  endo-cellular 
enzyme-like  substance  uninjured  and  active." 

I  have  quoted  Dr.  Levin's  own  phrase  as  to  the  use  of  auto- 
lyzed tissues,  chiefly  because  it  probably  expresses  the  general 
attitude  of  mind  of  experimenters  toward  this  particular  aspect 
of  the  subject,  in  that  it  inferentially  ascribes  the  immunizing 
influence  of  the  autolyzed  tissues  to  their  "enzyme-like  substance." 
It  is  hardly  necessary  to  tell  the  reader  of  the  present  monograph, 
however,  that  in  my  own  opinion  the  success  of  the  experiment 
was  due  not  to  the  presence  of  any  specific  enzymes,  but  to  the 
fact  that  the  tissue  used— cancer  tissue,  liver  tissue,  spleen,  blood, 
or  what  not — had  the  all-important  advantage  of  being  protein- 
bearing  tissue. 

This  conclusion,  to  be  sure,  is  inferential;  but  I  think  it  will 
be  admitted  to  find  strong  support  in  the  fact  that  all  manner  of 
tissues,  including  even  the  tissues  of  an  animal  of  another  species 
(mouse  tissues  introduced  into  the  rat,  for  example),  can  produce 
seemingly  the  same  condition  of  immunity. 

Note,  now,  the  very  significant  fact  that  when  a  dog  was  cured 
of  a  transplanted  tumor  by  the  transfusion  of  blood  of  an  im- 
mune animal  in  the  later  experiments  made  at  the  Loomis  Lab- 
oratory, it  was  shown  that  decompounding  and  absorption  of  the 
tumor  itself  was  an  essential  part  of  the  immunizing  process. 
This  was  proved  by  the  fact  that  it  was  not  found  possible  to 
render  a  dog  immune  to  transplantation  of  a  tumor  by  transfusing 
blood  before  such  transplantation.  It  was  only  after  the  tumor 
had  actually  been  transplanted  and  begun  its  growth,  that  the 
transfusion  sufficed,  through  the  process  of  destroying  the  tumor, 
to  give  the  animal  immunity  against  further  inoculation. 


ANIMAL  EXPERIMENTATION  AND  PROTEAL  THERAPY          291 

Perhaps  the  most  plausible  explanation  of  this  is  found  in  the 
suggestion  that  the  transfused  blood  contained  corpusclar  or  en- 
zymic  substances  that  could  begin  the  decompounding  of  the 
cancer  cell,  and  that  through  such  decompounding  a  stimulus  was 
given  to  the  blood-forming  organs  of  the  animal  that  led  to  an 
elaboration  of  the  defensive  mechanism  that  would  not  otherwise 
take  place.  The  permanent  modification  of  the  conditions  in  the 
dog's  system  that  made  it  resistant  to  future  inoculation  would 
thus  be  attributable  to  activities  stimulated  by  the  cancer  pro- 
teins, acting  virtually  as  autologou-s-  antigens. 

In  this  view  immunity  thus  .induced  is  closely  comparable  to 
immunity  induced  by  inoculation  wkh  autolyzed  tissues. 

No  doubt  it  has  occurred  to  a  large  number  of  workers,  that, 
as  Dr.  Levin  phrases  it,  "to  induce  en  immunity  to  cancer  growth 
may  indicate  the  way  to  rational  treatment  of  cancer,  since  such 
an  immunity  would  prevent  the  occurrence  of  metastases,  after 
the  primary  tumor  is  removed."  But  doubtless  most  such 
workers  have  felt,  as  Dr.  Levin  felt,  that  "it  is  self-evident  that 
the  results  obtained  cannot  be  transferred  as  yet  to  human 
pathology." 

Had  it  occurred  to  any  one,  however,  that  the  active  agent 
involved  was  merely  protein  matter  as  such,  and  not  enzymes 
specifically  associated  with  or  antagonistic  to  the  cancer  cell, 
there  would  have  been  no  such  embargo  on  transferring  the  re- 
search to  human  pathology. 

But  as  the  experimenters  failed  to  gain  this  conception,  the 
inviting  possibilities  were  unrealized,  and  the  clues  to  a  solution 
of  the  problem  were  found  in  a  quite  different  way.  I  have  told 
the  story  in  some  detail  elsewhere  and  4t  need  not  be  repeated 
here. 

THE  VALUE  OF  EARLY  TREATMENT 

Among  the  most  important  of  the  observations  of  the  animal 
experimenters,  in  their  possible  application  to  the  human  subjects, 
are  those  showing  that  (1)  there  is  a  marked  distinction  to  be 
drawn  between  the  original  susceptibility  of  an  animal  to  inocula- 
tion with  cancer  and  the  resistance  to  growth  of  the  tumor  in  the 
same  animal  at  a  later  period ;  and  (2)  the  correlated  fact  that  the 
same  tumor  appears  to  develop  increasing  virulence  as  it  is 
brought  through  section  and  transplantation  from  the  body  of 
one  animal  to  another. 

As  illustrating  the  first  point,  it  is  noted  that  a  pregnant  mouse 
is  very  insusceptible  to  inoculation  with  a  tumor  transplanted 
from  another  mouse,  yet  once  the  transplantation  has  been  suc- 
cessfully effected,  the  tumor  grows  with  extraordinary  vigor. 

A  possible  explanation  of  this  would  be  that  the  pregnant  ani- 
mal has  a  system  relatively  well  fortified  against  protein  invasion, 


292  THE  PROTEAL  TREATMENT  OF  CANCER 

due  to  the  fact  that  there  is  a  certain  amount  of  proteid  absorp- 
tion from  the  placenta  (the  experiments  of  Abderhelden  in  this 
connection  will  be  recalled),  which  led  to  a  leucocytosis,  and  to 
the  presence  of  an  increased  enzyme  titer  in  the  blood.  In  a  word, 
the  organism  is  well  equipped  to  fight  against  the  invasion  of  the 
protein  cells  represented  by  the  cancer  inoculation.  If,  however, 
in  spite  of  this  condition  of  preparedness,  the  cancer  cells  grow 
with  such  vigor  that  they  prevail  against  the  defending  host,  then 
it  is  not  surprising  that  they  take  on  very  rapid  development,  be- 
cause of  the  relatively  large  amount  of  nourishment  that  must  be 
present  in  the  blood  and  lymph  channels  of  the  pregnant  animal 
to  provide  for  the  growth  of  the  embryo. 

It  will  be  recalled  that  investigators  have  shown  the  chemical 
affinity  between  the  rapidly  growing  tumor  and  the  embryo — each 
of  them  containing  a  relatively  low  nitrogen  content.  In  a  sense, 
the  foetus  is  in  itself  a  foreign  tumor,  and  one  that  takes  on  ex- 
traordinary rapidity  of  growth.  Like  the  malignant  tumor,  the 
foetus  has  capacity  for  almost  indefinite  growth ;  and  were  it  not 
possible  presently  to  extrude  the  foetus  it  would  become  as  great 
a  menace  to  the  life  of  the  mother  as  the  cancer  itself.  That 
thought  need  not  be  expanded  here,  however.  From  the  present 
standpoint,  the  important  thing  is  to  recall  that  there  is  a  distinc- 
tion between  the  initial  resistance  to  the  early  growth  of  a  tumor 
and  subsequent  resistance  to  its  later  growth. 

It  is  probable  that  this  variation  is  not  due  solely  to  conditions 
in  the  system  of  the  animal,  but  that  it  is  also  dependent  in  part 
on  changed  conditions  of  the  tumor  itself.  This  idea  finds  strong 
support  in  the  observed  increasing  virulence  of  tumors  as  they 
pass  from  one  organism  to  another.  It  seems  plausible  to  sup- 
pose that  this  increasing  virulence  is  at  least  in  part  a  function 
of  age;  and  to  infer  from  this  that  cancer  tissues  in  the  same  in- 
dividual may  gain  increasing  virulence  as  they  grow  older.  The 
familiar  fact  that  cancer  cachexia  appears  only  at  the  later  stage 
of  development  of  the  malady  in  the  human  subject;  coupled  with 
the  fact  that  metastatic  secondary  tumors  very  commonly  grow 
with  exceptional  vigor,  gives  added  support  to  this  suggestion. 

The  obvious  application  of  this  line  of  reasoning  is  that  there 
is  an  enormous  premium  on  early  treatment  of  cancer  in  the  hu- 
man subject — not  merely  treatment  in  the  sense  of  cutting  out 
the  new  growth  as  soon  as  it  is  discovered — though  in  many  cases 
that  may  be  desirable — but  also  in  the  sense  of  fortifying  the  de- 
fensive mechanism  of  the  body  by  every  available  means.  There 
is  abundant  clinical  warrant  for  the  belief  that  the  protein  treat- 
ment, for  example,  may  accomplish  results  when  administered  to 
a  patient  having  a  new  cancerous  growth  that  could  not  be  hoped 
for  were  the  tumor  a  post-operative  recurrence ;  the  obvious  ex- 


ANIMAL  EXPERIMENTATION  AND  PROTEAL  THERAPY         293 

planation  being,  in  the  light  of  what  has  just  been  said,  that,  on 
one  hand,  the  new  tumor  is  probably  relatively  non-virulent  and, 
on  the  other  hand,  that  the  system  of  the  patient  has  not  had  time 
to  undergo  so  profound  a  condition  of  metabolic  disturbance  as 
accompanies  the  progress  of  the  malady. 

Results  attained  with  relative  ease  at  an  early  stage  become  al- 
most impossible  at  a  later  stage,  in  which  the  cancer  cells  were 
additionally  fortified  and  the  bodily  defenses  progressively  weak- 
ened. Stimulated  by  the  presence  of  the  abnormal  cells,  the 
blood-forming  mechanism  may  ultimately  reach  a  point  of  ex- 
haustion which  permits  only  a  feeble  response  to  new  proteins. 
Myelocytes,  leucoblasts  and  lymphoidocytes  take  the  place  of 
normal  large  monocytes;  normal  polymorphs  are  replaced  by 
those  of  small,  immature  type;  the  lymphocytes  are  devoid  of 
cytoplasm— a  "starved"  type;  the  red  cells  poikilocytic  or 
nucleated. 

This,  assuredly,  is  not  a  hopeful  picture.  Yet  even  under  such 
circumstances  modifications  in  the  blood  in  the  direction  of  nor- 
mality, and  corresponding  improvement  in  the  general  condition 
of  the  patient,  together  with  modifications  of  the  neoplasm,  are 
sometimes  effected  by  protein  treatment  within  a  relatively  brief 
period,  though  not  with  spectacular  suddenness.  In  one  of  my 
recent  cases  (No.  488),  for  example,  a  recurrent  cancer  of  the 
breast  rapidly  developing  about  one  year  after  removal,  the  blood 
count  before  treatment  showed  33  per  cent,  of  large  mononuclear 
leucocytes,  but  very  few  of  these  were  normal  monocytes,  the 
major  part  of  them  being  of  the  leucoblast  type.  In  the  san?e 
count  the  polynuclears  represented  53.3  per  cent,  and  the  small 
lymphocytes  only  8  per  cent.,  the  eosinophiles  4.9  per  cent. 

After  five  days'treatment  with  rape  protein,  there  was  a  very 
remarkable  transformation.  The  leucoblasts  had  disappeared,  pos- 
sibly being  transformed  into  polynuclears,  since  the  latter  now 
represented  69  per  cent,  of  the  white  cell  count.  Large  mono- 
nuclears  were  now  only  4.6  per  cent.,  but  these  were  of  the  normal 
type,  either  of  true  monocytes  with  large  nucleus  and  basic  cyto- 
plasm or  of  Ehrlich's  transitionals.  Meantime,  there  had  been, 
seemingly,  very  active  stimulation  of  the  lymphatic  system,  since 
the  small  lymphocytes  now  numbered  23.5  per  cent.  Many  of 
the  lymphocytes  were  fairly  large,  and  with  a  relatively  large 
amount  of  cytoplasm.  The  eosinophiles  were  now  only  1.5  per 
cent.,  but  there  were  granular  cells  that  stained  dark,  resembling 
the  eosinophiles  in  structure  rather  than  true  basophiles,  to  the 
additional  number  of  4.3  per  cent. 

After  another  interval  of  five  days,  the  leucocyte  count  had 
progressed  still  farther  in  the  direction  of  normality,  as  regards 
the  quality  of  the  cells,  the  typical  large  monocytes  now  num- 
bered 7.2  per  cent. ;  the  polynuclears  60.2  per  cent. ;  lymphocytes 


294 


THE   PROTEAL  TREATMENT   OF   CANCER 


TABLE   IX.— ORIGINAL  CASES 

A  GROUP  or  CASES  or  INOPERABLE  CANCER  STILL  UNDER  OBSERVATION  AND  IN  ROBUST 
CONDITION  AFTER  PROLONGED  PERIODS  or  PROTEAL  TREATMENT 
(251  TO  632  DAYS;  AVERAGE,  424  DAYS) 


1 

J 

Name 

Nature  of  Case 

1  No.  of  Days  II 

i 

Red 
Blood 
Corpus- 
cles 

White 
Blood 
Cor- 

s: 

ll 

a 

Mono- 
nuclears 

It 

SO 

Large 

Small 

278 

Mrs.  B  

Rec.  C.  of  Breast.  . 

105 

90 

4,400,000 

68.6 

19 

20.6 

1.6 

9 

180 

100 

5,408,000 

7,600 

72 

17.3 

8.6 

2 

0 

194 

100 

4,832,000 

6,100 

54.6 

34 

11.5 

0 

0 

475 

57.4 

13.7 

26.8 

1.7 

0.7 

16 

MiMD.... 

Rec.  C.  Of  Breast.  . 

93 

90 

4,464,000 

59 

17 

24 

0 

0 

198 

95 

5,664,000 

7,600 

66.5 

21.5 

20 

2 

0 

215 

100 

5,252,000 

7,600 

61.6 

13 

24 

1.5 

0 

627 

3,705,000 

6,240 

60 

13.3 

26.6 

0.6 

• 

881 

Mrs.  H.... 

Melanoma  

2 

100 

4,752,000 

7,600 

80.5 

7.6 

8.6 

8.3 

0 

16 

100 

4,448,000 

8,000 

78 

10.5 

7 

4.5 

0 

30 

100 

4,500,000 

8,200 

81 

12.5 

6 

1 

.5 

48 

100 

5,184,000 

8,000 

77.5 

9.5 

11 

2 

0 

324 

67.5 

21.5 

8.5 

.6 

1.5 

239 

Mrs.  M... 

Car.  of  Breast  

142 

90 

5,376,000 

7,200 

64.3 

16.3 

15.6 

3.6 

• 

156 

95 

4,800,000 

8,800 

62.3 

21.5 

13 

2 

1 

172 

100 

5,096,000 

siooo 

60 

23.5 

13 

2.5 

1 

405 

58 

16 

22 

4 

0 

870 

Mrg.R.... 

Ep.  Car.  of  Hand.. 

5 

95 

4,896,000 

10,200 

72.6 

14 

10.6 

2.6 

0 

20 

90 

4,556,000 

10,400 

74 

10 

12 

3.5 

Ji 

45 

90 

4,130,000 

12,000 

77.5 

16 

6.5 

1 

0 

811 

58.4 

30.3 

5.8 

5.4 

.1 

242 

Mrs.S  

Ep.  of  Face  

69 

75 

2,800,000 

60 

10.5 

29 

.5 

0 

144 

95 

4,672,000 

6,600 

65.5 

28 

14.5 

1 

155 

100 

4,672,000 

7,200 

60.6 

31 

15.5 

8 

• 

460 

51 

9 

38.5 

1.5 

882 

MrfcV.W. 

Rec.  C.  of  Breast.  . 

50 

85 

5,008,000 

8,880 

64 

16 

24 

0 

9 

62 

100 

4,522,000 

7,600 

58.6 

18.6 

19.3 

2.3 

I 

76 

100 

4,448,000 

7,400 

65 

17.6 

15 

2.6 

0 

90 

100 

5,656,000 

8,900 

48.5 

27 

20.6 

4 

0 

394 

39.3 

17.6 

41.6 

1.3 

0 

455 

100 

5,600,000 

6,900 

61 

29.5 

18.5 

1 

0 

605 

100 

5,610,000 

6,600 

168 

Miss  W.  .  . 

Rec.  C.  of  Breast.  . 

88 

80 

4,448,000 

66.3 

11.6 

20 

2 

0 

112 

95 

4,240,000 

8,000 

67.3 

21.6 

10 

.6 

.3 

121 

100 

4,650,000 

9,200 

64.5 

18 

17 

.6 

0 

486 

52.6 

20.3 

26 

1.3 

0 

251 

Mrs.W... 

Rec.  C.  of  Breast.  . 

632 
63 

100 
85 

5,177,000 
3,570,000 

9,100 

74 

11 

11 

4 

0 

138 

85 

5,280,000 

9.400 

68 

16 

9.5 

6.5 

0 

155 

95 

4,288,000 

8,600 

64.5 

19.6 

12 

8 

1 

467 

63.6 

9 

20 

6.6 

609 

6,044,000 

60.3 

8.3 

22.6 

8.8 

868 

MmC.... 

Rec.  C.  of  Breast.  . 

1 

90 

3,976,000 

9,330 

66.6 

14.3 

17.3 

2.3 

.3 

29 

95 

4,112,000 

8,500 

64.6 

19 

12.3 

3.6 

.3 

44 

100 

4,576,000 

8,900 

72 

14.5 

13 

.6 

0 

60 

100 

4,096,000 

8.000 

61.5 

19.5 

18 

1 

0 

312 

55.3 

16.6 

28.3 

2 

0 

643 

Mr.  P  

C.  of  Stomach.... 

0 

60 

4,956,000 

12,200 

57 

11 

30 

2 

0 

7 

75 

4,364,000 

8,500 

59.5 

19 

21.5 

0 

• 

17 

70 

4,012,000 

7,200 

24 

80 

4,974,200 

6,138 

29 

63.8 

18.5 

16.5 

1 

.5 

33 

80 

5,000,000 

6.900 

50 

25.6 

23.6 

.6 

41 

85 

4,938,000 

8,800 

228 

4,644,000 

8,200 

70 

12.5 

12.5 

4.6 

243 

85 

4,848,000 

9,600 

261 

4,320,000 

6,400 

ANIMAL  EXPERIMENTATION  AND  PROTEAL  THERAPY          295 

24.4  per  cent. ;  eosinophiles  5.6  per  cent. ;  basophiles  1.2  per  cent. 
At  this  time  study  of  the  red  cells  showed  a  great  abundance 
of  normoblasts  and  free  microblasts.  Two  weeks  later,  however, 
these  had  altogether  disappeared  (October  18th).  The  large 
monocytes,  of  normal  type,  now  numbered  9.6  per  cent. ;  the  poly- 
morphs  stood  practically  unchanged  at  59.6  per  cent. ;  the  lym- 
phocytes had  fallen  to  19.6  per  cent.,  and  there  were  only  1  per 
cent,  each  of  eosinophiles  and  basophiles.  A  month  later  (No- 
vember 16th),  the  count  showed  continued  progress,  the  poly- 
nuclears  having  fallen  to  55.3  per  cent.,  whereas  large  mononu- 
clears  had  risen  to  13.3  per  cent.,  small  lymphocytes  to  27.3  per 
cent.,  and  eosinophiles  to  4  per  cent. 

The  significant  feature  of  this  blood  modification  was  the 
transformation  from  abnormal  types  to  normal  types  of  large 
mononuclears  and  the  very  notable  increase  of  lymphocytes.  The 
patient's  general  condition  had  meantime  improved  and  there  was 
a  tendency  to  softening  of  the  tumor  mass  in  the  breast,  flattening 
of  a  large  lymph  node  in  the  axilla,  and  marked  regression  of  a 
subclavicular  mass.  It  was  not  to  be  expected,  however  that  very 
marked  regression  of  the  tumor  would  occur  until  the  large  mono- 
cyte  count  had  been  brought  to  a  much  higher  state.  The  ulti- 
mate result  must  be  left  for  future  record.  I  mention  the  case 
here  merely  to  illustrate  a  rather  exceptional  modification  of  the 
blood  count,  and  to  emphasize  the  point  that  in  a  case  of  such 
chronicity,  in  which  the  lymphatic  system  is  seriously  involved, 
with  metastases,  one  must  be  content  to  go  slowly,  expecting  no 
such  spectacular  metamorphosis  as  was  recorded  in  the  letter 
above  quoted. 

By  way  of  contrast,  note  the  progress  of  another  recent  case 
(No.  497)  in  which  there  was  primary  involvement  of  both 
breasts  not  far  advanced.  A  surgeon  had  advised  removal  of  both 
breasts,  yet  malignancy  was  considered  doubtful  by  me  until  the 
blood  count  showed  the  following :  polynuclears,  48.9  per  cent. ; 
large  mononuclears  (including  myelocytes),  16.6  per  cent.;  small 
lymphocytes,  30.5  per  cent.;  eosinophiles,  4  per  cent.  The  re- 
sponse to  the  proteal  treatment  was  immediate;  the  patient  re- 
ported a  transformation  in  general  health,  and  the  blood  count 
after  three  weeks  of  treatment  (November  16,  1916)  was:  poly- 
nuclears, 43.6  per  cent. ;  large  monocytes,  21  per  cent. ;  small  lym- 
phocytes, 33.6  per  cent.;  eosinophiles,  1.6  per  cent. 

The  rapid  response  of  this  patient  as  contrasted  with  the  pre- 
ceding one  may  be  ascribed,  in  all  probability,  to  the  early  stage 
of  development  of  the  neoplastic  growths. 

With  the  emphasizing  of  this  point,  I  may  perhaps  advantage- 
ously leave  this  aspect  of  the  subject,  reiterating  the  opinion  that: 
here,  as  in  so  many  other  fields  of  pathology,  there  is  a  tremen- 


296  THE   PROTEAL  TREATMENT  OF   CANCER 

dous  premium  on  early  treatment.  Proteal  remedies  have  indeed 
proved  capable  of  giving,  solace  in  extraordinary  measure  to  late 
stage  inoperable  cases  of  the  most  hopeless  type;  but  the  full 
measure  of  what  may  be  expected  of  the  new  treatment  can  be 
gauged  only  when  the  Proteals  have  been  administered  to  a  large 
number  of  cases  at  an  earlier  stage  of  development. 


SECTION  XI 
THE  PREVENTION  AND  CURE  OF  CANCER 

If  the  essential  thesis  of  this  paper  as  to  the  nature  of  cancer 
is  accepted,  and  it  is  further  accepted  that  the  administration  of 
vegetable  proteins  hypodermically  tends  to  stimulate  the  enzymes 
capable  of  protein  hydrolysis,  certain  practical  suggestions  as  to 
the  prevention  of  cancer;  as  to  possible  cure  of  the  cancerous 
condition ;  and  as  to  the  obviation  of  its  recurrence,  follow  almost 
as  matters  of  course. 

Since,  however,  things  that  seem  obvious  after  one  has  devoted 
much  thought  to  a  subject  are  not  always  quite  so  plain  to  those 
who  have  thought  along  different  lines,  perhaps  it  may  not  be 
amiss  to  present  here,  partly  by  way  of  summary  and  recapitula- 
tion, a  brief  practical  discussion  of  the  prevention  and  the  pos- 
sible cure  of  the  condition  which  I  have  characterized  as  hyper- 
proteomorphism,  with  particular  reference  to  that  phase  of  the 
condition  characterized  by  the  presence  of  a  malignant  neoplasm 
or  true  cancer. 

As  to  prevention,  I  shall  speak  only  in  the  briefest  terms. 
Whatever  tends  to  maintain  the  general  good  health,  keep  the 
blood  count  normal,  promote  the  normal  digestion  and  nutrition, 
and  keep  the  muscles  (including  those  of  the  arterial  walls)  plas- 
tic, tends  to  ward  off  the  cancerous  condition. 

No  single  expedient,  in  my  judgment,  is  more  important  than 
habitual  and  vigorous  exercise,  particularly  for  persons  in  middle 
life  and  (modified  in  intensity)  in  old  age.  Keep  the  muscular 
system  in  really  vigorous  condition ;  avoid  excess  proteins  in  the 
food,  in  particular  animal  proteins ;  drink  plenty  of  water ;  avoid 
all  sources  of  general  systemic  irritation  as  well  as  local  irritation, 
and  there  is  at  least  a  large  measure  of  probability  that  the  can- 
cerous condition  will  never  develop. 

Once  it  has  developed,  however,  and  in  particular  when  it  has 
formed  a  local  neoplasm  of  the  type  that  we  term  epithelioma, 
carcinoma,  or  sarcoma,  as  the  case  may  be,  is  there  a  possibility 
of  a  cure  of  the  condition? 


THE  PREVENTION  AND  CURE  OF  CANCER  297 

The  answer  must  be,  I  think,  that  there  is  nothing  inherent  in 
the  nature  of  the  malady  that  makes  it  necessarily  fatal  (the  re- 
sults of  animal  experimentation  appear  to  justify  this  verdict)  ; 
but  that,  on  the  other  hand,  it  is  implied  in  the  very  nature  of 
the  condition  that  unless  there  can  be  a  radical  readjustment  of 
the  relations  of  the  individual  to  his  environment,  the  case  is 
hopeless. 

Merely  to  cut  out  the  local  neoplasm,  and  hope  thus  to  cure 
the  disease,  is  a  childish  procedure.  The  surgeon  tells  you  that  if 
you  make  the  incision  early  enough  and  radical  enough,  all  will 
be  well.  But,  of  course,  you  can  never  make  the  incision  early 
enough  nor  radical  enough.  You  could,  to  be  sure,  eradicate 
cancer  of  the  uterus  by  universal  hysterectomy  in  childhood,  and 
annul  cancer  of  the  breast  by  universal  amputation  of  infantile 
mammae.  But  such  a  procedure  would  have  no  conspicuous  bear- 
ing on  the  cancerous  condition,  and  would  not  in  any  way  shield 
the  organs  that  remained. 

It  is  true  that  most  surgeons  claim  a  considerable  proportion 
of  "cures"  following  their  operative  procedures,  particularly  for 
cancer  of  the  breast.  But  very  few  surgeons  have  cared  to  pub- 
lish statistics  as  to  the  post-operative  history  of  their  cases,  ex- 
tending over  a  term  of  years.  One  surgeon  of  my  personal  ac- 
quaintance admits  that  when  he  attempted  to  follow  up  his  cases 
he  found  that  very  few  indeed  were  living  three  years  after  the 
operation,  and  only  a  single  case  after  a  lapse  of  five  years. 

Whether  or  not  we  accept  that  as  a  typical  experience,  it  will 
be  denied  by  no  one  that  the  usual  and,  so  to  say,  expected  his- 
tory of  a  cancer  case  after  operation  is  characterized  by  meta- 
static  recurrence ;  that  after  a  second  and  perhaps  a  third  opera- 
tion the  case  reaches  an  inoperable  stage;  and  that  inoperable 
cancer  is  universally  regarded  as  among  the  most  hopeless  of 
conditions. 

Speaking  with  the  utmost  conservatism,  we  can  now  say  that 
experience  justifies  the  statement  that  the  Proteal  treatment  has 
come  with  at  least  a  message  of  hope  for  these  supposedly  hope- 
less cases.  As  regards  actual  and  permanent  eradication  of  the 
diseased  condition,  doubtless  this  applies  to  only  a  small  percen- 
tage of  the  cases  hitherto  treated  by  the  new  method.  But  that 
is  merely  equivalent  to  saying  that  the  major  part  of  the  cases 
thus  treated  have  been  individuals  whose  systems  were  in  so 
profound  a  state  of  disrepair  that  in  the  nature  of  the  case  they 
could  not  be  mended. 

Researches  at  the  Mayo  Clinic  have  made  it  clear  to  what  an 
alarming  extent  changes  that  may  be  considered  cancerous  in 
character  occur  in  other  organs  of  the  body  than  those  directly 
effected  either  by  the  original  neoplasm  or  by  definite  metastases. 


298  THE  PROTEAL  TREATMENT  OF  CANCER 

These  observations  are  obviously  in  keeping  with  the  present 
thesis  as  to  the  general  character  of  the  cancerous  condition. 
They  accord  also  with  a  wide  range  of  clinical  experience.  It  is 
almost  axiomatic  to  say  that  no  two  cases  could  be  precisely  alike 
as  to  the  exact  degree  of  involvement  of  the  various  organs  and 
tissues  of  the  body.  Inherent  susceptibilities  of  hereditary  char- 
acter, combined  with  accidental  conditions  of  local  irritation, 
would  determine  that  in  one  case  the  liver,  in  another  the  pan- 
creas, in  a  third  the  kidneys  would  have  suffered  most  from  the 
condition  of  nutritional  maladjustments,  in  a  series  of  cases  in  all 
of  which  the  seat  of  the  "primary  cancer"  might  be,  let  us  say, 
the  breast,  the  stomach,  or  the  uterus. 

It  is  equally  axiomatic  to  say  that  the  precise  location  of  me- 
tastatic  masses  and  the  precise  relative  degree  of  involvement  of 
various  organs  affected  without  metastasis  must  be  vastly  im- 
portant in  its  bearing  on  the  prognosis  of  the  case  as  regards  im- 
minence of  the  fatal  issue. 

Obviously,  then,  each  case  must  be  a  law  unto  itself.  If  it  is 
hazardous  to  generalize  regarding  conditions  described  merely  as 
"cancer  of  the  breast,"  "cancer  of  the  uterus,"  etc.,  it  is  equally 
hazardous  to  attempt  predictions  as  to  the  possible  curability  of 
any  individual  case  thus  described. 

No  one  speaking  with  authority  in  connection  with  the  Proteal 
treatment  ever  made  such-  a  prediction  or  held  out  the  expectation 
of  cure  in  any  individual  case.  From  the  outset,  in  my  publica- 
tions and  medical  addresses  on-  the  subject,  I  have  urged  that  a 
conservative  attitude  must  be  maintained  as  regards  ultimate 
prognosis. 

No  one  speaking  with  authority  has  suggested  or  expected  that 
the  proteins  would  perform  the  necromantic  feat  of  restoring  de- 
generated and  decompounded  cells  of  liver  or  spleen  or  kidneys 
or  pancreas  or  intestinal  glands.  As  well  ask  the  surgeon  to  re- 
place a  lost  arm  or  leg.  Yet  without  such  regeneration,  in  a  large 
proportion  of  cases,  it  would  be  utterly  futile  to  hope  for  the 
restoration  of  normal  conditions  of  protein  metabolism  absolutely 
essential  to  health. 

If,  in  such  a  case,  the  Proteal  -treatment  favorably  modified  the 
blood  count  and  made  possible  a  temporary  improvement  in 
metabolism,  thereby  relieving  the  patient's  distress,  nullifying 
the  obnoxious  odors  of  a  cancerous  -discharge,  inducing  a  sense  of 
well  being,  and  prolonging  life  by  a  term  of  weeks  or  months 
while  at  the  same  time  giving  comfort — everything  has  been  ac- 
complished that  could  rationally  be  expected ;  everything,  perhaps, 
that  can  never  -be  hoped  for  in  connection  with  the  treatment  of 
cases  at  so  advanced  a  stage. 

It  should  be  added,  however,  that  it  is  seldom  possible  to  de- 


THE   PREVENTION    AND   CURE   OF   CANCER  299 

termine  with  accuracy  the  precise  stage  of  advancement  of  any 
given  case,  for  the  obvious  reason  that  we  cannot  examine  the 
structure  of  the  various  organs  even  if  quantitative  tests  of  their 
degree  of  involvement  were  available.  A  case  that  seems  pro- 
foundly cachectic,  and  even  almost  moribund,  may  in  reality  have 
tissues  less  vitally  involved  than  those  of  another  case  that  has 
been  tangibly  affected  for  a  much  briefer  period  and  in  which  the 
visible  symptoms  seem  less  alarming. 

Hence  it  occasionally  happens  that  a  case  in  which  the  most 
optimistic  estimate  of  a  skilled  observer  would  predict  a  very  early 
demise  responds  to  the  treatment  with  unexpected  vigor  and  ral- 
lies in  a  way  which  enthusiastic  observers  have  not  hesitated  to 
speak  of  as  "almost  miraculous." 

In  a  considerable  number  'of  instances,  cases  of  this  character 
have  gone  on,  under  the  Proteal  treatment,  to  a  stage  of  improve- 
ment which  may  with  validity  be  spoken  of  as  clinical  recovery. 
Whether  or  not  the  conditions  of  bodily  metabolism  have  been 
permanently  readjusted  in  such  wise  that  the  proliferation  of  mis- 
placed cells  will  be  prevented  in  future,  must  be  left  to  the  future 
to  decide. 

It  may  fairly  be  said,  I  think,  that  where  a  cancerous  mass  has 
thus  retrogressed  under  the  Proteal  treatment  there  is  greater 
inherent  probability  of  non-recurrence  than  if  it  had  disappeared 
under  local  treatment  or  through  surgical  interference ;  inasmuch 
as  an  improved  condition  of  general  bodily  metabolism  is  implied 
in  the  results  attained  by  the  hypodermic  method. 

When  treatment  consisting  exclusively  of  hypodermic  injection 
into  the  tissue  of  the  upper  arm  has  resulted  in  the  regression  of  a 
tumor  mass  in  the  pelvis,  no  argument  is  required  to  show  that 
there  has  been  profound  modification  of  the  condition  of  the  body 
fluids.  It  is  perhaps  permissible  to  hope  that  this  modification 
may  have  an  element  of  permanency,  or  that  it  may  be  kept  up 
by  occasional  administration  of  the  hypodermic  remedy,  and  that 
recurrence  or  metastasis  of  the  localized  cancerous  mass  will  thus 
be  prevented. 

I  repeat,  that  this  is  a  matter  for  the  future  to  decide.  But  I 
would  suggest  also  that  every  practitioner  who  has  successfully 
treated  a  case  with  Proteals  should  feel  it  incumbent  upon  him 
to  urge  his  patient  to  have  a  blood  count  made  at  intervals  of 
two  or  three  months  so  long  as  he  lives,  and  to  submit  himself 
to  a  new  course  of  treatment  should  the  blood  show  the  slightest 
deviation  from  the  standard.  Doubtless  it  would  be  safer  to  take 
an  occasional  course  of  the  treatment  whatever  the  blood  condi- 
tions. In  any  event,  the  treatment  should  not  be  discontinued  for 
a  good  many  weeks  after  the  disappearance  of  the  neoplasm. 

That  there  should  be  most  careful  attention  to  the  diet  with 


300  THE   PROTEAL   TREATMENT   OF   CANCER 

particular  reference  to  the  nitrogen  balance,  goes  without  saying. 
Careful  attention  should  be  given  to  all  hygienic  measures  tend- 
ing to  promote  general  health.  But  in  particular  a  regime  of  life 
should  be  adopted  that  includes  daily  systemic  exercise  of  the 
most  vigorous  type  consistent  with  the  patient's  condition  of 
muscular  tract.  In  my  opinion,  no  single  measure  is  more  im- 
portant than  this ;  indeed,  no  other  measure  except  that  concern- 
ing the  protein  diet,  approaches  it  in  importance. 

But  these,  after  all,  are  matters  regarding  which  the  wise  physi- 
cian scarcely  needs  counseling.  When  it  is  clearly  apprehended 
that  the  cancerous  condition  is  due  to  a  maladjustment  of  protein 
metabolism,  it  follows  as  a  matter  of  course  that  all  the  measures 
commonly  recognized  as  tending  to  reestablish  the  normal  adjust- 
ment of  such  metabolism  must  be,  in  the  first  instance,  preventa- 
tive  of  cancer ;  in  the  second  instance,  invaluable  as  auxilliaries 
during  the  treatment  of  the  malady,  by  whatever  method;  and, 
in  the  third  place,  indispensable  as  measures  directed  against  re- 
currence of  the  malady. 

But  while  all  this,  stated  in  general  terms,  seems  fairly  axio- 
matic, there  goes  with  the  suggestion  the  implication  that  no  type 
of  malady  could  give  greater  opportunity  for  the  exercise  of  pro- 
fessional skill  than  the  treatment  of  the  cancerous  condition.  I 
have  urged  the  futility  of  surgical  treatment  which  is  content 
merely  to  wield  the  knife  and  disregard  all  general  measures.  I 
would  now  urge  that  it  would  be  only  a  degree  less  fatuous  to 
suppose  that  adequate  treatment  of  a  cancer  case  by  the  protein 
method  implies  merely  the  random  administration  of  a  hypo- 
dermic. Yet  a  -good  many  physicians  who  have  used  proteins  have 
seemed  to  labor  under  this  misapprehension.  The  correspondence 
is  filled  with  letters  from  physicians  of  acknowledged  standing 
who  state  that  they  have  administered  a  dozen  ampules,  or  two 
dozen  ampules,  of  Proteals  with  remarkable  results,  and  who  now 
wish  to  ask  if  it  is  necessary  to  continue  treatment. 

A  typical  instance  of  -this  kind  concerned  a  case  of  uterine  can- 
cer, originally  operated  upon  and,  after  recurrence,  pronounced 
inoperable  at  one  of  our  most  important  metropolitan  cancer  hos- 
pitals, and  subsequently  radiumed  without  benefit  and  pronounced 
hopeless.  Proteals  had  been  turned  to  as  a  last  resort,  and 
eighteen  doses  had  been  administered  in  a  term  of  about  six 
weeks.  And  then  the  physician,  without  show  of  emotion,  calmly 
inquires  whether  there  is  any  necessity  for  further  treatment, — a 
cure  having  seemingly  been  effected ! 

Needless  to  say  the  physician  was  urged  to  continue  the  treat- 
ment. 

I  cite  this  instance  as  illustrating  how  vague  may  be  the  con- 
ception of  the  true  character  of  cancer  in  the  minds  of  well-in- 


THE  PREVENTION  AND  CURE  OF  CANCER  301 

formed  physicians.  Perhaps  this  is  not  surprising,  considering 
that  the  available  authorities  differ  so  widely  in  their  estimate  of 
the  nature  of  cancer.  The  fact  that  Metchnikoff  advocated  the 
theory  of  the  germ  origin  of  cancer  no  doubt  has  "had  great 
weight ;  and  doubtless  there  are  physicians  who,  in  accepting  this 
view,  and  having  also  in  mind  the  conceivability  of  destroying 
disease  germs  at  a  single  dose,  or  at  the  most  with  two  or  three 
doses,  as  was  at  first  expected  of  Salvarsan,  have  thought  that 
the  Proteals  might  act  in  similar  manner.  Their  expectations  seem 
to  be  justified  when  the  administration  of  two  or  three  doses  pro- 
duces very  striking  modification  in  symptoms,  including  change 
in  the  character  of  the  discharge,  and  a  softening  and  tendency 
to  regress  in  the  neoplasm  itself. 

Even  were  cancer  a  germ  disease  (which  I  altogether  disbe- 
lieve), and  were  it  therefore  possible  to  conceive  a  treatment  that 
would  eradicate  the  cause  of  the  disease  at  a  single  coup,  by  the 
slaughter  of  bacteria,  there  would  still  remain  the  neoplasm  itself, 
a  proteid  mass,  to  deal  with.  To  expect  that  medication  of  any 
character  would  lead  to  the  dissolution  of  the  mass,  when  it  is  a 
large  one,  without  profound  systematic  disturbance  would  be  to 
misconceive  the  nature  of  the  essential  physiological  conditions. 
It  is  neither  to  be  expected  nor  desired  that  the  protein  matter 
making  up  the  cancer  should  be  hydrolyzed  all  at  once,  nor  even 
with  great  rapidity.  Were  the  enzymic  attack  on  the  cancer  cells 
too  active,  the  blood  must  become  charged  with  the  products  of 
protein  decompounding,  and  a  tax  would  be  put  upon  the  cerebral 
tissues  and  the  organs  of  elimination  that  they  might  not  be  able 
to  withstand. 

It  follows  that  the  carrying  of  a  case  of  cancer  under  the  pro- 
teal  treatment  to  a  favorable  issue,  even  in  the  least  complicated 
cases,  is  a  matter  demanding  full  measure  of  professional  skill. 
I  recall  once  hearing  a  somewhat  distinguished  artist  say  that  any- 
one can  begin  the  painting  of  a  picture,  but  that  it  takes  an  artist 
to  finish  it.  Similarly  it  may  be  said  that  any  one  can  begin  the 
proteal  treatment  of  a  case  of  cancer.  Whoever  can  administer 
a  hypodermic  with  ordinary  aseptic  precautions  can  secure  defi- 
nite results  that  are  conspicuous  and  even  notable  in  a  great  ma- 
jority of  cases.  But  to  carry  the  case  forward  so  that  the  effects 
are  cumulative,  and  ultimately  to  secure  the  largest  measure  of 
benefit  possible,  requires  skill  of  a  high  order. 

If  the  best  possible  results  are  to  be  attained,  it  will  be  neces- 
sary not  only  to  administer  the  treatment  with  constant  observa- 
tion of  results  as  a  guide  to  dosage  and  frequency  of  administra- 
tion and  the  shifting  from  one  proteal  to  another ;  but  also  to  in- 
voke, in  many  cases,  the  aid  of  supplementary  measures. 

First  and  foremost  among  these  supplementary  measures,  is 


302  THE   PROTEAL   TREATMENT   OF   CANCER 

the  knife  of  the  surgeon.  It  is  true  that  the  Proteals  have  hitherto 
been  applied  almost  exclusively  in  inoperable  cases.  But  in  more 
than  one  instance  it  has  happened  that,  under  the  influence  of  the 
remedy,  a  cancerous  mass  too  widely  extended  for  removal  has 
regressed  until  the  remaining  mass  is  readily  operable.  In  such  a 
case,  I  would  strongly  urge  that  the  co-operation  of  the  surgeon 
should  be  sought,  and  the  mass  excised.  By  so  doing,  we  relieve 
the  system  of  the  patient  of  the  burden  of  absorption  of  a  mass 
of  protein  tissue. 

It  will  not  usually  be  necessary,  however,  to  make  the  surgical 
operation  so  radical,  when  Proteals  are  used,  as  it  otherwise  must 
be ;  inasmuch  as  the  metastatic  glands  and  the  neighboring  tissues 
— which  at  best  the  surgeon  can  remove  but  inadequately — are 
peculiarly  subject  to  the  proteolytic  enzymes  evoked  by  the  ad- 
ministration of  the  hypodermic  remedy. 

It  goes  without  saying,  now  that  Proteal  therapy  supplies  a 
means  hitherto  not  available,  to  stimulate  the  production  of  the 
blood  corpuscles  and  whip  up  their  enzyme-forming  capacities, 
that  no  surgeon  of  judgment  will  think  of  performing  an  opera- 
tion for  cancer  without  supplementing  his  surgical  procedure  with 
the  use  of  Proteal  remedies  before  and  for  some  time  after  the 
operation. 

It  is  essential,  of  course,  to  bear  in  mind  the  familiar  phenom- 
ena of  anaphylaxis,  and  to  continue  the  administration  of  any 
given  protein  daily,  or  at  intervals  of  two  or  three  days  at  the 
most,  until  immunization  is  attained.  It  would  obviously  be  in- 
advisable, after  administering  a  given  protein,  to  wait  ten  days 
or  two  weeks  before  administering  a  second  dose  of  the  same 
protein ;  since  it  is  precisely  under  such  conditions  that  the  phe- 
nomena of  anaphylaxis  in  its  alarming  form  are  likely  to  be 
developed.  One  protein,  as  is  well  known,  does  not  fully  im- 
munize the  system  against  another.  Indeed,  it  is  precisely  this 
fact,  as  already  pointed  out,  that  furnished  the  basis  for  the 
theoretical  administration  of  a  series  of  proteins  along  the  lines 
just  suggested. 

It  has  been  pointed  out  that  there  is  a  wide  range  of  variation 
among  patients  as  regards  their  response  to  a  given  quantity  of 
any  foreign  protein.  The  degree  of  susceptibility  of  individual 
patients  must  be  determined  by  experiment. 

It  should  be  recalled,  however,  that  in  giving  maximum  doses 
one  is  introducing  a  relatively  large  quantity  of  foreign  proteins 
and  that  these  proteins  must  be  dealt  with  by  the  bodily  enzymes. 
So  it  may  be  accepted  as  a  general  principle  of  medication  that 
the  smallest  dose  that  will  produce  a  vigorous  enzymic  (corpus- 
cular) response  is  the  best  dose. 

There  may  come  a  time  in  the  course  of  any  individual  case, 


THE   PREVENTION   AND   CURE   OF   CANCER  303 

at  which  the  enzymic  response  has  reached  the  maximum.  If, 
then,  the  administration  of  large  doses  of  Proteals  is  continued 
at  short  intervals,  the  demands  put  upon  the  corpuscles  in  dealing 
with  the  proteins  thus  introduced  may  exhaust  their  resources, 
tending  to  induce  a  condition  of  pernicious  anaemia. 

The  rational  procedure  in  such  a  case  is  to  discontinue  for  a 
time  the  administration  of  the  protein  to  which  the  body  has 
become  "immunized" ;  either  giving  no  treatment  at  all  for  a  time 
(days  or  weeks,  according  to  the  progress  of  the  case),  or  else 
substituting  small  doses  of  different  proteins.  In  either  case,  the 
dose  of  the  original  protein  should  be  small  when  its  use  is 
resumed.  Patients  who  had  discontinued  the  treatment  for  a 
term  of  weeks  have  repeatedly  been  observed,  on  resumption  of 
the  treatment,  to  react  as  vigorously  to  the  small  doses  as  if 
taking  it  for  the  first  time. 

From  all  this  it  will  appear  that  no  mere  rule  of  thumb  can  be 
applied  in  determining  the  dosage,  interval  of  administration,  or 
length  of  treatment  with  protein  antigens  of  any  individual  case 
of  cancer.  In  general,  it  may  be  said  that  the  dose  to  be  aimed 
at  is  that  which  will  carry  the  red  blood  count  and  the  haemo- 
globin test  to  the  normal,  and  keep  the  large  mononuclear  leuco- 
cytes in  adequate  cohorts. 

It  should  be  recalled  that  no  treatment  can  hope  to  produce 
better  general  systemic  conditions  than  the  individual  patient  ex- 
perienced during  his  normal  life;  hence  that  every  one  who  has 
suffered  from  cancer  must  always  be  more  or  less  liable  to  recur- 
rence,— unless,  indeed,  it  should  ultimately  be  shown  that  a  meas- 
ure of  immunity  results  from  regression  of  the  neoplasm. 

In  other  words,  the  cancer  would  not  originally  have  developed 
had  there  not  been  certain  inherent  defects  in  the  bodily  mech- 
anism of  the  individual.  Often  these  defects  are  hereditary. 
Usually  they  are  associated  with  the  on-coming  of  old  age,  prema- 
ture or  otherwise.  They  mark  a  condition  in  which  the  capacity 
of  the  organism  to  deal  with  protein  metabolism  is  waning.  So 
this  individual  will  probably  always  need  the  prop  of  an  artificial 
stimulant  to  the  cytogenic  apparatus  from  time  to  time.  Proteals 
supply  such  a  prop.  Their  use  will  probably  become  routine  prac- 
tice not  only  in  the  post-operative  treatment  of  cancer  subjects, 
but  in  the  after-year  treatment  of  cases  that  have  had  the  neo- 
plasms removed  by  the  action  of  Proteals  themselves. 

Obviously  the  same  thing  applies  to  cases  treated  successfully 
with  X-ray  and  radium. 

In  a  word,  it  may  be  expected  that  the  province  of  Proteal 
therapy  will  be  by  no  means  confined  to  the  treatment  of  cancer, 
but  will  have  a  place  at  least  as  important,  and  conceivably  more 
important,  in  the  prevention  of  recurrence  after  the  local  neoplasm 


304  THE   PROTEAL  TREATMENT   OF   CANCER 

has  been  removed  by  any  means  whatsoever ;  and,  ultimately  also, 
no  doubt,  in  prophylaxis  applied  to  any  person  who  through  mal- 
nutrition, combined  with  some  local  source  of  irritation,  has  rea- 
son to  fear  the  development  of  cancer. 

Meantime  this  method  gives  to  the  individual  cancer  sufferer, 
whatever  the  stage  of  his  malady,  and  to  the  physician  who  is 
called  upon  to  treat  him,  the  most  enheartening  message  of  hope 
that  pres«nt-day  therapeutics  can  offer. 


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